Why whales are big but not bigger: Physiological drivers and ecological limits in the age of ocean giants.

The largest animals are marine filter feeders, but the underlying mechanism of their large size remains unexplained. We measured feeding performance and prey quality to demonstrate how whale gigantism is driven by the interplay of prey abundance and harvesting mechanisms that increase prey capture rates and energy intake. The foraging efficiency of toothed whales that feed on single prey is constrained by the abundance of large prey, whereas filter-feeding baleen whales seasonally exploit vast swarms of small prey at high efficiencies. Given temporally and spatially aggregated prey, filter feeding provides an evolutionary pathway to extremes in body size that are not available to lineages that must feed on one prey at a time. Maximum size in filter feeders is likely constrained by prey availability across space and time.

Comparison of postoperative headache after retrosigmoid approach: vestibular nerve section versus vestibular schwannoma resection.

OBJECTIVE: To evaluate intradural drilling as a mechanism for the development of postoperative headache after retrosigmoid craniectomy. STUDY DESIGN: A retrospective review of charts was performed on 565 retrosigmoid approaches to the cerebellopontine angle performed between January 1980 and January 1998. Patients treated with retrosigmoid vestibular nerve section without intradural drilling were compared with patients who underwent retrosigmoid removal of vestibular schwannomas in which intradural drilling was performed for exposure of the internal auditory canal. SETTING: Private practice tertiary referral center. PATIENTS: Consecutive patients undergoing retrosigmoid approach between January 1980 and January 1998 were reviewed. MAIN OUTCOME MEASURES: The presence of headache, duration of headache, and severity of headache were noted. RESULTS: In this large series, 54% of patients experienced headaches after vestibular schwannoma removal, and 5% of patients experienced headaches after vestibular nerve section (p < 0.01, chi-square). CONCLUSIONS: Postoperative headache is not a characteristic of retrosigmoid craniectomy in the absence of intradural drilling. Intradural drilling is a probable cause of headache after the retrosigmoid approach. Cranioplasty is not necessary to prevent a high incidence of postoperative headache after retrosigmoid approach.

Medical treatment of headache after suboccipital acoustic tumor removal.

OBJECTIVES: Suboccipital craniotomy is a frequently used surgical approach for removal of cerebellopontine angle (CPA) tumors. A frequently cited consequence, however, is the high incidence of postoperative headaches. Much has been written regarding prevention of these headaches, but little has been written of their treatment. The authors review their extensive experience in suboccipital tumor removal and the medical management of postoperative headache, highlighting the recent use of a regimen of divalproex sodium and verapamil. STUDY DESIGN: Retrospective chart review. METHODS: The charts of a consecutive series of patients having suboccipital craniotomies for CPA tumors were reviewed. Presence, duration, and severity of headache were noted. Medical treatments and their effectiveness were also noted. RESULTS: Between 1980 and 1997, 228 patients underwent suboccipital craniotomy for removal of CPA tumors. Of these patients, 124 (54.4%) complained of headache. For 62 (27.2%) the headaches persisted for more than a year after surgery. Twenty-nine patients (12.7%) received no relief from any medication. Ten of these patients received a regimen of divalproex sodium and verapamil, with all patients obtaining significant relief. CONCLUSION: Headache is a significant problem with the suboccipital approach for acoustic tumor removal. The majority of patients that complain of headache can be adequately treated with nonsteroidal anti-inflammatory drugs (NSAIDs). If pain is unrelieved by NSAIDs, treatment becomes problematic. The authors' early experience with divalproex sodium/verapamil is encouraging and deserves further investigation as a treatment for these refractory cases.

Surgical techniques for cochlear implantation in the very young child.

Early cochlear implantation to treat prelingually deafened children has been shown to improve speech perception and overall performance. The current age limit for implantation is 24 months in accordance with US Food and Drug Administration guidelines, but it is believed that earlier implantation is possible and may result in better performance. Implantation in children younger than 36 months, however, is complicated by the altered anatomy of the temporal bone in this young age group. We have developed specific modifications in the cochlear implantation technique for this young age group. This technique was used in implantation for 17 children younger than 36 months. The ages ranged from 16 to 36 months and averaged 30 months. All patients except one had complete electrode insertion without complication. The technique of cochlear implantation must be modified not only for differences in anatomy in these young children but also for the expected continued growth of the temporal bone and related structures. Cochlear implantation can be safely performed on children as young as 16 months.

Canalplasty.

Canal stenosis and atresia can result from a number of causes, including congenital, inflammatory, neoplastic and iatrogenic pathologic conditions. Canalplasty is an eclectic collection of techniques designed to recreate a patent and trouble-free external canal. Despite the large number of etiologies, the principles of canalplasty are the same. The goal is the creation of a widely patent and physiologically intact canal wall. Both the bony and cartilaginous portions must be addressed surgically. Care should be taken to preserve the normal skin and adnexa for lining the canal, but if this is not adequate, skin grafts should be used to prevent healing by secondary intent. Overcorrection of stenosis is advised. We have presented our basic technique for canalplasty and discussed its alteration for specific disorders.

Pediatric cholesteatoma: an individualized, single-stage approach.

We report our experience with a one-stage surgery for pediatric cholesteatoma in 216 ears. Our technique is based on three main principles: (1) the surgery is individualized; (2) the goal of surgery is to completely remove cholesteatoma and related disease in one operation; and (3) the reconstruction is performed to provide both good hearing and a dry, trouble-free ear. The incidence of recidivism was 10.2%, and the rate achieved was 13.3% at 5 years and 24% at 10 years. Canal wall down surgery was the predominant procedure used. The incidence of intraoperative neurosensory hearing loss, vertigo, and facial nerve injury was extremely low. The postoperative cavity problems encountered were minimal.

Prognostic implications of large volume residual disease in patients with advanced stage epithelial ovarian cancer.

Thirty-two patients with Stage III or IV epithelial ovarian cancer and residual tumor volumes in excess of 2 cm in diameter after initial debulking were treated with platinum and cyclophosphamide chemotherapy. Twenty-seven patients (84%) received at least six courses of chemotherapy. Six patients developed grade 3 or 4 hematologic toxicity and one patient died with granulocytopenia and sepsis. The actuarial survival of the total group of patients was 78% at 12 months, 27% at 24 months, and 11% at 36 month. Of patients with residual disease 2-4 cm in diameter, 82% were alive 12 months after diagnosis and 46% were alive at 24 months. In contrast, patients with greater than 4 cm residual disease had a 12-month survival of 73% and a 24-month survival of only 7%. The size of residual tumor after surgery remains a very important prognostic factor in patients treated with platinum-based combination chemotherapy. Reoperation with further tumor debulking should be considered in ovarian cancer patients referred for chemotherapy with large volume residual disease to maximize response to combination chemotherapy.

Oncostatin M: a growth regulator produced by differentiated histiocytic lymphoma cells.

A polypeptide termed oncostatin M, which inhibits the replication of A375 melanoma and other human tumor cells, but not normal human fibroblasts, has been isolated from serum-free supernatants of U-937 histiocytic lymphoma cells that have been induced to differentiate into macrophage-like cells following treatment with the phorbol ester phorbol 12-myristate 13-acetate. No such growth inhibitory activity is detected in the supernatant of untreated U-937 cells, indicating that the protein is induced or increased in expression in the phorbol ester-induced differentiated cells. Oncostatin M is stable between pH 2 and 11 and after heating for 1 hr at 56 degrees C but is not stable at 90 degrees C. Purification of oncostatin M has been achieved by gel chromatography and reversed-phase HPLC, using sequentially acetonitrile and n-propanol in the presence of aqueous trifluoroacetic acid. The apparent molecular weight of oncostatin M is approximately 18,000, as determined by gel chromatography, and 28,000, as determined by polyacrylamide gel electrophoresis. The amino-terminal amino acid sequence of the purified polypeptide has been determined. No substantial sequence homology between oncostatin M and other proteins was found, including other tumor cell inhibitory proteins produced by mononuclear cells. Oncostatin M, therefore, appears to represent a distinct cell growth regulator.

Phase II clinical trial using californium 252 fast neutron brachytherapy, external pelvic radiation, and extrafascial hysterectomy in the treatment of bulky, barrel-shaped stage IB cervical cancer.

From June 1977 to June 1983, 32 patients with bulky (greater than 4 cm diameter), barrel-shaped Stage IB cervical cancer were treated at the University of Kentucky Medical Center by a combination of outpatient neutron brachytherapy using californium 252 (252Cf) and external pelvic radiation followed by extrafascial hysterectomy. Nineteen patients had cervical tumors 4 to 6 cm in diameter, and 13 patients had lesions in excess of 6 cm in diameter. A dose of 4500 rad external photon therapy was given from a linear accelerator, and one or two 6-hour 252Cf implants were given during or immediately after external radiation. Extrafascial hysterectomy with bilateral salpingo-oophorectomy was performed 6 weeks after completion of radiation therapy. Complications during and after radiation were minimal and included vaginal stenosis (three) and proctitis (two). Tumor clearance in the hysterectomy specimen was complete in 23 patients (72%) and residual cervical tumor was present in 9 patients (28%). Two patients developed tumor recurrence and died of disease 15 and 27 months after therapy, respectively. Thirty patients remain free of disease 26 to 96 months (median, 52 months) after treatment, and none have been lost to follow-up. The actuarial survival of these patients is 97% at 2 years and 94% at 5 years. Intracavitary neutron therapy is well tolerated and is effective when combined with external radiation and hysterectomy in the treatment of bulky, barrel-shaped Stage IB cervical cancer.

Adjuvant vincristine, dactinomycin, and cyclophosphamide therapy in stage I uterine sarcomas. A pilot study.

Seven patients with Stage I uterine sarcomas (greater than or equal to 10 mitoses/10 high-power fields) were treated with surgery plus adjuvant vincristine, dactinomycin, and cyclophosphamide (VAC) chemotherapy in a pilot study conducted at the University of Kentucky Medical Center from 1978 to 1983. Surgery consisted of total abdominal hysterectomy, bilateral salpingo-oophorectomy, and para-aortic lymph node sampling. Chemotherapy was begun within 1 week of surgery, and all patients received at least six monthly courses of VAC. This chemotherapeutic regimen was well-tolerated, and toxicity was minimal. Two patients had recurrent sarcoma, and one of them has died of disease. The remaining five patients are alive and well with no evidence of disease 48 to 73 months after therapy. The recurrence rate of patients with Stage I uterine sarcomas treated with adjuvant VAC chemotherapy was significantly (P less than 0.02) less than that for similar patients treated at this institution (1964-1977) by surgery alone or surgery plus pelvic radiation. These results suggest that primary adjuvant chemotherapy is beneficial in patients with Stage I uterine sarcomas.

Programming for the DNA analysis of FCM data on an IBM microcomputer.

The analysis of data generated on a flow cytometer (FCM) is often performed on a computer obtained especially for dedicated use with the flow cytometer. This computer component can be expensive and also presents the FCM user with the added burden of mastering specialized programming language or of accepting the secret analytical processes of protected proprietary program routines. We believe that the evolution of more accurate and efficient FCM analyses that have the power to consider complex signal distributions can be assisted by the availability of analysis programs written in languages common to many users. DNA analysis routines written for a relatively inexpensive microcomputer (IBM PC/XT) in Basic and Pascal are described here. The routines can automatically process multiple FCM data files and can provide high-resolution graphic hardcopy. A foreground/background utilization is also described that allows the computer to be available for other uses in the laboratory.

Treatment of cervical intraepithelial neoplasia III by hysterectomy without intervening conization in patients with adequate colposcopy.

One hundred forty-four patients found to have cervical intraepithelial neoplasia (CIN) III on colposcopically directed biopsy who had completed childbearing were treated with a vaginal hysterectomy (112 patients) or abdominal hysterectomy (32 patients). The mean age of these patients was 28.6 years and the mean gravidity, 3.4. All patients had adequate colposcopy of the cervix and vagina. The transformation zone and lesion(s) were completely visualized. The uterus was submitted for histologic examination in all cases. The cervix was sectioned in a radial fashion (minimum 12 sections), and the proximal endocervix and lower uterine segment were sectioned transversely. CIN III was present in the cervix of 117 patients, CIN II in 9 patients, CIN I in 8 patients, and no evidence of residual neoplasia in 9 patients. Microinvasive cancer (1.3 mm stromal invasion without lymph-vascular space invasion) was present in one patient. After surgery, patients were seen every 3 months for 2 years and every 6 months thereafter. All 144 patients were followed up for at least 12 months, 124 patients for 24 months, 103 patients for 36 months, and 60 patients for 60 to 120 months. To date, all patients are alive and well and there have been no cases of recurrent vaginal neoplasia or cancer. These data suggest that: adequate colposcopy is an accurate method to rule out invasive cervical cancer and abdominal or vaginal hysterectomy is an effective therapeutic procedure in women with CIN III who have completed reproductive function.

Hydrodynamic characterizations of estrogen receptors complexed with [3H]-4-hydroxytamoxifen: evidence in support of contrasting receptor transitions mediated by different ligands.

Size-exclusion high-performance liquid chromatography was used to characterize the hydrodynamic molecular properties of estrogen receptors complexed with estradiol and the antiestrogen 4-hydroxytamoxifen. Cytoplasmic estrogen receptors complexed with [3H]-4-hydroxytamoxifen did not undergo reductions in hydrodynamic size after exposure to KCl or urea. Nuclear receptors complexed with 4-hydroxytamoxifen eluted as hydrodynamically larger molecules than nuclear receptors complexed with estradiol. Because identical hydrodynamic characterizations were obtained with the covalent ligand [3H]tamoxifen aziridine, these differences in chromatographic behavior are due to differences in ligand-mediated receptor properties and are not the result of ligand dissociation. When estrogen receptors, complexed with either [3H]estradiol or [3H]-4-hydroxytamoxifen, were exposed to trypsin, the receptors complexed with 4-hydroxytamoxifen eluted as larger hydrodynamic forms than receptors complexed with estradiol. These observations are interpreted to indicate that estradiol and 4-hydroxytamoxifen mediate contrasting transitions in the molecular orientation of estrogen receptors. The consequences of the transitions mediated by 4-hydroxytamoxifen appear to be that intermolecular associations become difficult to disrupt with KCl or urea and that the accessibility of trypsin-sensitive proteolytic sites becomes altered. Chromatin fractionation using DNase I and hypotonic Mg2+ solubilization identified a chromatin region that was less readily penetrated by receptors complexed with 4-hydroxytamoxifen than receptors complexed with estradiol.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined radiation therapy and extra-fascial hysterectomy in the treatment of stage IB barrel-shaped cervical cancer.

Seventy-five patients with bulky barrel-shaped Stage IB cervical cancers, treated at the University of Kentucky from 1965 to 1981, were the subjects of this investigation. Thirty-two of these patients were treated with radiation therapy alone and 43 were treated with radiation followed by extra-fascial hysterectomy. There were no significant differences in age, gravidity, or tumor cell type between the two treatment groups. Patients were seen at regular intervals from 2 to 11 years after treatment and none were lost to follow-up. Recurrent cancer was noted in 47% of patients treated by radiation alone as compared to 16% of those treated with combined therapy (P less than 0.01). The incidence of pelvic recurrence was reduced from 19% to 2% and extrapelvic recurrence from 16% to 7% in patients treated by combination therapy. No rectal or urinary tract fistulae were noted after extra-fascial hysterectomy. The findings of this study suggest that the use of extra-fascial hysterectomy following radiation therapy in patients with bulky Stage IB cervical cancer causes a significant reduction in tumor recurrence without producing an increase in treatment-related complications.

The prognostic significance of lymph-vascular space invasion in stage I endometrial cancer.

Surgical specimens from 111 patients with Stage I endometrial cancer were reviewed for the presence of lymph-vascular space invasion by tumor cells. Lymph-vascular space invasion was noted in 16 cases, and occurred most frequently in poorly differentiated tumors with deep myometrial penetration. Tumor recurrence developed in 44% of patients whose tumors demonstrated lymph-vascular space invasion as opposed to only 2% of patients without this finding (p less than 0.001). Of seven patients with lymph-vascular space invasion who experienced tumor recurrence, five developed extra-pelvic metastases. Discriminant function analysis of these data revealed a statistically significant correlation between lymph-vascular space invasion and tumor recurrence, independent of histologic differentiation of myometrial penetration. These findings suggest that lymph-vascular space invasion by tumor cells is an important prognostic variable in Stage I endometrial cancer which should be considered in treatment planning.

Steroid receptor analysis by size-exclusion liquid chromatography: considerations for the clinical laboratory.

Steroid receptor activity can be more quickly estimated by size-exclusion chromatography than by conventional analysis on sucrose gradients, and profiles of receptor activity are better resolved. Here we discuss several factors affecting this form of analysis in clinical laboratories. The composition of the elution buffer influences steroid receptor elution and recovery: high ionic strength, neutral pH, and the presence of dimethylformamide are important. Of the TSK-SW (Beckman) size-exclusion chromatographic columns we considered, the TSK-G2000SW column appeared to be the most appropriate. "Reference" elution profiles are presented for several marker proteins and estrogen receptor forms generated under different sample-treatment conditions. In examining the sensitivity of receptor analyses by this method, we used fresh rodent preparations, a commercial receptor reference (Estrocept), and human tumor material obtained by needle biopsy. We also compared frozen and lyophilized receptor preparations with fresh ones.

Esterase activity, exclusion of propidium iodide, and proliferation in tumor cells exposed to anticancer agents: phenomena relevant to chemosensitivity determinations.

Cellular esterase activity and the ability to exclude propidium iodide were examined after exposing tumor cells to anticancer agents. In general, esterase activity and the ability to exclude propidium iodide continued when cells proliferated and disappeared when proliferation was inhibited. However, with a number of preparations, drug exposure inhibited proliferation while esterase activity and propidium iodide exclusion persisted. These indications of persisting cell function or viability after drug exposure may be relevant to a potential for tumor cell recovery. When the viability of established cell lines progressively declined on days 4 and 7 following drug exposure, recovery did not occur. When proliferative recoveries occurred, viabilities remained elevated. Estimates of in vitro sensitivity by proliferation-related criteria were contrasted by persistent high viability estimates in 22% of the determinations performed with primary tumor cell preparations. The potential for recovery may explain the disappointing ability of proliferative chemosensitivity assays to predict clinical sensitivity.

Estrogenicity of coumestrol in the mouse: fluorescence detection of interaction with estrogen receptors.

The estrogenicity of coumestrol, a fluorescent phytoestrogen, has been examined in murine uteri. Coumestrol competed with 17 beta-[3H]estradiol for binding to cytoplasmic estrogen receptors, caused cytoplasmic estrogen receptors to associate with chromatin in the nucleus, and induced progesterone receptors. By use of size-exclusion high-performance liquid chromatography (SEHPLC), the interaction of coumestrol with estrogen receptors was examined directly by monitoring the fluorescence associated with macromolecules having properties characteristic of estrogen receptors. These analyses were made possible by the addition of dimethylformamide to the elution buffer, at a concentration (7.5%) which improved recoveries but did not interfere with estrogen receptor binding. It was possible to detect fluorescent coumestrol at approximately 0.5 nM. All determinations were performed with preparations in which estrogen receptor activity was 3-10 nM. Exposure of these preparations to coumestrol (50 nM) resulted in the elution of increased fluorescent activity in the regions where estrogen receptors eluted during SEHPLC. This fluorescent activity was reduced when diethylstilbestrol, 17 beta-estradiol, hexestrol, or tamoxifen was present as a competitor (2 microM) but was unaffected by testosterone or progesterone. Diethylstilbestrol reduced fluorescence below endogenous base lines and thereby displayed a fluorescence quench property which was not observed with other ligands. When hepatic and renal estrogen receptor preparations were used, the injected receptor activity was observed to be the major limiting factor in detecting the interaction of coumestrol with estrogen receptors. These observations are relevant to attempts to visualize estrogen receptors in tumor cells and demonstrate that accepted biochemical criteria for ligand-receptor interaction can be satisfied when fluorescent ligands are examined.

Immunohistochemical localization of tumor markers in epithelial ovarian cancer.

Immunohistochemical determinations of carcinoembryonic antigen, alpha-fetoprotein, human chorionic gonadotropin (hCG), and human placental lactogen (hPL) were performed on tissue sections from 137 epithelial ovarian cancers. Fewer than 25% of serous cystadenocarcinomas contained detectable amounts of any marker. Carcinoembryonic antigen was present in over 50% of tumors, and was noted most frequently in mucinous, endometrioid, and clear cell carcinomas. hPL was demonstrated in 30% of endometrioid carcinomas but was rarely present in other cell types. Both alpha-fetoprotein and hCG were noted in fewer than 10% of all major cell types of epithelial ovarian cancer. Forty-five patients had serial determinations of plasma levels of carcinoembryonic antigen at the time of regular follow-up visits. Serial plasma levels of carcinoembryonic antigen accurately predicated recurrence in nine of 16 patients whose tumors contained carcinoembryonic antigen, in contrast to two of 16 patients whose tumors were devoid of antigen.