Biomedical subjects
L A Newman
Publications and source records attributed to L A Newman.
Occurrence of the chromoplast protein ChrA correlates with a fruit-color gene in Capsicum annuum.
Plant geneticists have determined that the color of ripe fruits of sweet peppers (Capsicum annuum L.) is determined by four genes: y, c1, c2 and cl. We have compared the electrophoretic behavior of chromoplast membrane proteins of seven varieties of C. annuum which differ in these genes. ChrA was detected only in the varieties that had a y+ genotype, and was not affected by variations in the other three genes. The identity of ChrA was verified by probing blots of SDS gels with antiserum to ChrA. The second known chromoplast-specific protein, ChrB, was found to be independent of all four genes. No proteins correlating with c1, c2 or cl were detected in either one- or two-dimensional gels.
External cephalic version with ruptured membranes and adequate amniotic fluid volume.
The use of external cephalic version in the patient with ruptured membranes is examined and the first successful reported case is described. No difficulties or complications were encountered. We conclude that use of this procedure in the presence of ruptured membranes has been unjustly slighted and that external version may offer an important alternative to the patient with ruptured membranes, adequate amniotic fluid, and malpresentation. We caution that this should only be attempted under continuous monitoring, in patients with adequate amniotic fluid, and in facilities where immediate cesarean section is available. We believe that a larger trial is warranted, and we encourage that this be done.
Videofluoroscopic analysis of the infant swallow.
A better understanding of the abnormal infant swallowing mechanism requires better knowledge of the normal infant swallow. Twenty-one full-term infants under six months of age were examined using videofluoroscopy of the swallowing portion of upper gastrointestinal examinations. Components of the oral and pharyngeal stages of swallowing were evaluated. Results showed high reliability between two raters in obtaining measurement data. There was variability in suck and oral transit time, which was correlated to the number of sucks per swallow. All infants appeared to move their tongue in a "stripping" motion, and collected the material in various sites in the oral cavity or oropharynx before initiation of the swallow. The incidence of nasopharyngeal reflux was low (9.5%). The majority of infants demonstrated a slight residue in their valleculae and hesitation in the cervical esophagus. These findings indicate that videofluoroscopy provides an objective and systematic method for analyzing the infant swallowing mechanism.
Vaginal birth after cesarean delivery: results of a 5-year multicenter collaborative study.
Cesarean delivery has become the most frequently performed major operation in the United States. Widespread use of vaginal birth after previous cesarean delivery could potentially eliminate up to one-third of cesareans. However, many physicians have been reluctant to adopt this policy without large studies conclusively demonstrating its safety. This study evaluated the maternal and perinatal outcomes of over 5000 cases of labor after previous cesarean delivery. This multicenter study began in 1984 and initially included nine California hospitals. During the first 2 years, there were 1776 trials of labor resulting in 1314 vaginal births. In January 1986 two additional hospitals joined the collaborative project. Over the next 3 years, there were 3957 trials of labor resulting in 2977 vaginal births at the 11 participating hospitals. During the entire study period, 5733 patients opted for a trial of labor and 4291 (75%) delivered vaginally. There were no maternal deaths in the trial-of-labor group, and perinatal mortality was not significantly different from that of the general obstetric population. These results support the findings of numerous smaller studies that have concluded that the policy of routine repeat cesarean delivery should be abandoned.
ChrA Is a Carotenoid-Binding Protein in Chromoplasts of Capsicum annuum.
Chromoplasts of Capsicum annuum var Albino contain a carotenoid-protein complex, which migrates as a brilliant orange band in gels under conditions of nondenaturing electrophoresis. In a second, denaturing separation, the complex resolves into a principal protein (ChrA) of 58 kilodaltons and several minor proteins of 20 to 55 kilodaltons, which may be adventitiously associated. Analysis of Western blots of both one- and two-dimensional gels showed that the principal protein component of the carotenoid complex is ChrA, a protein previously shown to be located specifically in chromoplast membranes. The identification of ChrA as a carotenoid-binding protein appears to be the first instance of a nonthylakoid, carotenoid-binding protein in higher plants.
Synthesis of Two Chromoplast-Specific Proteins During Fruit Development in Capsicum annuum.
The time-course of accumuiation of two membrane proteins during fruit ripening was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blots in tissue extracts of Capsicum annuum L., vars Emerald Giant, Albino, and DNAP VS-12. The proteins, named ChrA and ChrB, were previously shown to occur specifically in chromoplasts. Fruit development was divided into five stages based on changes in color. ChrA was not detectable in the first three stages, but accumulated to a high level in the fully mature, red fruit. ChrB was not detectable in the first, mature-green stage of fruit maturation, but was found in the second stage, when carotenoid accumulation first appeared, and in all later stages. The patterns of accumulation in chromoplasts that develop from proplastids or leucoplasts are similar to those in chromoplasts that develop from chloroplasts. We conclude that ChrA and ChrB are probably synthesized de novo during chromoplast development.
A comparison of early and delayed induction of labor with spontaneous rupture of membranes at term.
The management of women with spontaneous rupture of membranes at term in the absence of labor and with a cervix unfavorable for induction of labor is controversial. In this randomized study of 182 patients, we report the effects of delayed versus early induction of labor on maternal and neonatal outcome. Qualifying patients not in labor at 6 hours after spontaneous rupture of membranes were randomized to either immediate oxytocin induction (86 women) or expectant management with oxytocin induction at 24 hours if labor had not occurred spontaneously (96 women). The cesarean section rate did not differ between the two groups. Women in the delayed group had significantly longer hospitalization (P less than .003), and their infants were significantly more likely to receive antibiotics (P = .006). Infectious morbidity (positive cultures or x-ray-documented pneumonia) occurred in five of the neonates in the delayed group, all of whose mothers had an initial digital cervical examination, but in none of the neonates in the early group, a difference that did not reach statistical significance (P = .061). Five (28%) of 18 infants from the delayed group whose mothers had received an initial digital cervical examination became infected, compared with none of the 78 infants from the delayed group whose mothers did not have digital examinations (P less than .001). We conclude that there is no advantage to delaying induction of labor when women present at term with spontaneous rupture of membranes.
Vaginal birth after cesarean section: results of a multicenter study.
Cesarean section is now the most frequently performed major operation in the United States. Nearly one out of every four American babies is delivered by this operation. "Elective repeat" has become the most common indication for cesarean section. Although the safety of vaginal birth after cesarean section has been documented in several recent publications, automatic repeat cesarean section remains the rule in this country. We present one of the largest series of trial of labor ever reported. Of 57,553 live births, 4929 (8.6%) were of women with prior cesarean sections. Among 1776 patients who underwent a trial of labor, 1314 (74%) delivered vaginally. There was no maternal or perinatal mortality related to uterine scar rupture. Thus during the study period 1314 major operations were avoided. We conclude that, for the vast majority of women, allowing a trial of labor is a safe alternative to automatic elective repeat cesarean section.
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Presentation, treatment, and outcome of local recurrence afterskin-sparing mastectomy and immediate breast reconstruction.
BACKGROUND: The local recurrence (LR) rate with skin-sparing mastectomy (SSM) and immediate breast reconstruction (IBR) has been reported as comparable to the LR rate after conventional mastectomy. However, limited data are available on the prognostic significance and management of LR following SSM. METHODS: A prospective database maintained at the University of Texas M. D. Anderson Cancer Center identified 437 SSMs performed for 372 invasive T1/T2 breast cancers between 1986 and 1993. RESULTS: Twenty-three LRs were identified, with a LR rate of 6.2% (23/372). Twenty-two of these (96%) presented as palpable skin-flap masses. The median time to recurrence was 25 months (range, 3 to 98 months). Fourteen patients were treated with a combination of surgery and systemic therapy. Resection of the reconstructed breast was performed in only three patients. Complete local control of the recurrent disease was achieved in 17 patients (74%). Nine patients (39%) developed distant metastatic disease. At a median follow-up of 26 months, 14 of 23 patients (61%) are alive without evidence of disease, and 7 (30%) have died from breast cancer. CONCLUSIONS: Because LR rate with SSM is low and likelihood of local control and survival is high, SSM and IBR is an acceptable treatment option for early stage breast cancer.
Local recurrence and survival among black women with early-stage breast cancer treated with breast-conservation therapy or mastectomy.
BACKGROUND: Black women with breast cancer have significantly worse survival rates and receive diagnoses at relatively younger ages, compared with white patients with breast cancer, in the United States. Young age at diagnosis has been associated with increased risk for local recurrence (LR) after breast-conservation therapy (BCT). The goal of this study was to evaluate the impact of age and BCT on LR and survival rates among black patients with breast cancer. METHODS: The records for 363 black women treated for breast cancer (excluding stage IV disease) at a comprehensive cancer center were reviewed. RESULTS: Fifty-eight percent of patients (n = 211) had tumors < or = 5 cm in diameter. Forty-two of these patients (19.9%) received BCT; the LR rate for this group was 9.8%. A total of 168 patients (79.6%) underwent mastectomy; the LR rate for this group was 8.9%. Data on the primary operation were unavailable for one patient. Five-year disease-free survival rates were similar for patients treated with BCT and those treated with mastectomy (88% and 73%, respectively). LR was associated with significant decreases in 5-year overall survival rates for both the BCT group (67% vs. 95%, P < .01) and the mastectomy group (43% vs. 76%, P < .01). LR and 5-year disease-specific survival rates were similar for patients <50 years of age and patients > or = 50 years of age, regardless of treatment. CONCLUSIONS: LR and survival rates are not compromised by the use of BCT among black American patients. LR is associated with an increased risk of breast cancer death, regardless of treatment type. Younger age at diagnosis was not associated with an increased rate of LR after BCT in this series.
Feasibility of immediate breast reconstruction for locally advanced breast cancer.
BACKGROUND: Immediate breast reconstruction (IBR) has been considered contraindicated for patients with locally advanced breast cancer (LABC). Our goal was to determine whether IBR resulted in delayed postoperative chemotherapy, increased postoperative complications, or increased risk of recurrent disease. METHODS: A prospective database of 540 modified radical mastectomies performed with IBR between 1990 and 1993 identified 50 patients with LABC. Postoperative management and outcome were compared to that of 72 patients undergoing modified radical mastectomy without IBR treated on a standardized LABC protocol using preoperative chemotherapy, postoperative chemotherapy, and radiotherapy during the same time period. RESULTS: Results were evaluated by chi2 analysis. The median ages for the patients with IBR versus those not undergoing IBR were 44 and 46 years, respectively. The stage distribution for the IBR patients versus patients not undergoing IBR was as follows: IIB, 46% versus 17%; IIIA, 44% versus 39%; and IIIB, 10% versus 44%. The types of IBR were transverse rectus abdominis myocutaneous (TRAM) flap (68%), latissimus dorsi flap (2%), and implants (30%). Chemotherapy was given to all IBR patients: 24% preoperatively and 96% postoperatively. Radiotherapy was used in 40%. Four postoperative complications (8%) necessitated prolongation of hospitalization, including two patients requiring surgical debridement for partial flap loss; there were no complete flap losses. The incidences of major and minor wound complications in the group not undergoing IBR were 7% and 4%, respectively. Of the 15 patients receiving implant reconstruction, 7 (47%) required subsequent implant removal because of contractures or infections. The median interval between surgery and postoperative chemotherapy was 35 days for the IBR patients and 21 days for the patients not undergoing IBR. This difference was marginally significant (P =.05). With a median follow-up of 58.4 months, no significant differences in local or distant relapse rates were detected. CONCLUSIONS: IBR can be performed with low morbidity in patients with LABC. Use of autogenous tissue is preferable because of poor results with implants. IBR is associated with somewhat longer intervals to resumption of postoperative chemotherapy, but this does not appear to be clinically significant-the local and distant relapse rates are similar for LABC patients undergoing modified radical mastectomy with or without IBR.
Hand grip dynamometry as a predictor of postoperative complications reappraisal using age standardized grip strengths.
A mechanical hand grip dynamometer was used to derive age- and sex-related standard grip strengths from 247 healthy volunteers between 16 and 95 yr old. Preoperative grip strength was measured in 90 patients and related to postoperative complication rates. A grip strength of 85% standard for age and sex was found to be the most effective cut-off for prediction of postoperative complications in terms of sensitivity and specificity, predicting 74% of the complications (p less than 0.05). Specificity is improved over previously published standards related to sex alone especially when assessing the elderly patient (50% vs 21%). A grip strength below the recommended cut-off for age and sex suggests that the patient is in a high-risk group and demands further investigation of nutritional status. Studies of pre-operative nutritional support for the at risk group need to be undertaken.
Radiofrequency ablation of solid tumors.
Radiofrequency ablation of solid tumors is produced by frictional heating caused when ions in the tissue attempt to follow the changing directions of a high-frequency alternating current. The radiofrequency probe is typically placed under ultrasound guidance, and the ablation is performed with real-time ultrasound monitoring. Radiofrequency ablation has been demonstrated to be effective in the treatment of unresectable hepatic tumors, and promising results have also been obtained in tumors of the lung, bone, brain, kidney, prostate gland, and pancreas. Most recently, radiofrequency ablation has been tested in the treatment of invasive breast tumors. A preliminary study reported that intraoperative radiofrequency ablation causes invasive breast cancer cell death in patients with locally advanced breast cancer. An ongoing study is investigating the use of radiofrequency ablation for the treatment of breast tumors 2 cm or less in diameter.
Pathologic tumor response in the breast following neoadjuvant chemotherapy predicts axillary lymph node status.
PURPOSE: Neoadjuvant chemotherapy is becoming the standard of care for locally advanced breast cancer. This study was performed to determine whether pathologic primary tumor response to neoadjuvant chemotherapy might predict axillary lymph node status and so be used to identify patients in whom surgery could be effectively limited to biopsy of the previous primary tumor site without axillary dissection. PATIENTS AND METHODS: Between 1992 and 1996, 170 consecutive patients with locally advanced breast cancer were treated in a prospective trial with four preoperative cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide. Disease was staged before initiation of preoperative chemotherapy and before surgery. Segmental resection with axillary lymph node dissection or modified radical mastectomy was performed first, followed by postoperative chemotherapy and radiation therapy of the breast (or chest wall) and regional lymphatics. Patient and tumor characteristics associated with complete versus incomplete pathologic primary tumor response to neoadjuvant chemotherapy and correlation between primary breast tumor pathologic response and axillary lymph node status found at surgery were analyzed. RESULTS: Of 156 evaluable patients, 30 patients (19%) had primary breast tumors that were completely eliminated after induction chemotherapy based on histologic assessment. Nineteen of those 30 patients (63%) had negative axillary lymph nodes at dissection, compared with 13 patients (33%) of the 40 who had a near-complete pathologic primary tumor response (< or = 1 cm3 remaining) and only 15 patients (17%) of the 86 who had > 1 cm3 tumor remaining in the pathology specimen of the breast primary. Of the 22 patients with a complete pathologic response in the breast and a clinically negative axilla after induction chemotherapy, axillary dissection revealed positive lymph nodes in four. These four patients had only one or two positive lymph nodes. DISCUSSION: Because initial clinical regression of primary tumor with neoadjuvant chemotherapy is considered an excellent prognostic indicator and because patients with locally advanced breast cancer routinely receive local and regional radiation treatment followed by additional chemotherapy, the role of breast and axillary surgery has been questioned. In this study, a complete pathologic response of the primary tumor to induction chemotherapy is highly predictive of negative axillary lymph node status. Therefore, axillary lymph node dissection may be omitted in certain subsets of patients who have a biopsy-proven complete pathologic response in the primary tumor and a clinical negative axillary examination. Further prospective, randomized investigation is needed to confirm this finding.