Transferrin D1: identity in Australian aborigines and American Negroes.

Human transferrin D(1) obtained from an Australian aborigine was found to have the same substitution of glycine for aspartic acid in peptide 1C previously shown in transferrin D(1) from an American Negro. This finding is relevant to formation of distinct Australoid and African populations.

Dry potato extracts improve water holding capacity, shelf life, and sensory characteristics of fresh and precooked beef patties.

The objective was to examine shelf stability, cooked product yield, and sensory characteristics of beef patties that had no binder (Control), incorporated soy flour (Textured Vegetable Protein; TVP) or one of three dry potato extracts: X-TRATOS™ (potato extract), X-TRATOS™ O (potato extract with mustard), or X-TRATOS™ W (potato extract with sodium acid pyrophosphate). In retail display patties, all binders decreased discoloration and lipid oxidation compared to Control, and X-TRATOS™ O was superior (P < 0.05) to all other treatments. Cooking yield was higher (P < 0.05) in patties containing potato extracts compared with patties containing TVP, which had higher yield than Control patties. Beef patties with potato extracts were juicier (P < 0.05) than Control and TVP patties and had higher (P < 0.05) overall acceptability than Control patties. We conclude that potato extracts are effective binders for use in fresh or precooked beef patties because they improve retail shelf life, cooked product yield, and sensory characteristics.

Stable Transmission of Borrelia burgdorferi Sensu Stricto on the Outer Banks of North Carolina.

The spirochaete (Borrelia burgdorferi) associated with Lyme disease was detected in questing ticks and rodents during a period of 18 years, 1991-2009, at five locations on the Outer Banks of North Carolina. The black-legged tick (Ixodes scapularis) was collected at varied intervals between 1991 and 2009 and examined for B. burgdorferi. The white-footed mouse (Peromyscus leucopus), house mouse (Mus musculus) marsh rice rat (Oryzomys palustris), marsh rabbit (Sylvilagus palustris), eastern cottontail (Sylvilagus floridanus) and six-lined racerunner (Cnemidophorus sexlineatus) were live-trapped, and their tissues cultured to isolate spirochaetes. Borrelia burgdorferi isolates were obtained from questing adult I. scapularis and engorged I. scapularis removed from P. leucopus, O. palustris and S. floridanus. The prevalence of B. burgdorferi infection was variable at different times and sites ranging from 7 to 14% of examined questing I. scapularis. Mitochondrial (16S) rRNA gene phylogenetic analysis from 65 adult I. scapularis identified 12 haplotypes in two major clades. Nine haplotypes were associated with northern/Midwestern I. scapularis populations and three with southern I. scapularis populations. Sixteen isolates obtained from tick hosts in 2005 were confirmed to be B. burgdorferi by amplifying and sequencing of 16S rRNA and 5S-23S intergenic spacer fragments. The sequences had 98-99% identity to B. burgdorferi sensu stricto strains B31, JD1 and M11p. Taken together, these studies indicate that B. burgdorferi sensu stricto is endemic in questing I. scapularis and mammalian tick hosts on the Outer Banks of North Carolina.

Up-regulation of LFA-1 allows liver-resident memory T cells to patrol and remain in the hepatic sinusoids.

Liver-resident CD8+ T cells are highly motile cells that patrol the vasculature and provide protection against liver pathogens. A key question is: how can these liver CD8+ T cells be simultaneously present in the circulation and tissue-resident? Because liver-resident T cells do not express CD103 - a key integrin for T cell residence in epithelial tissues - we investigated other candidate adhesion molecules. Using intra-vital imaging we found that CD8+ T cell patrolling in the hepatic sinusoids is dependent upon LFA-1-ICAM-1 interactions. Interestingly, liver-resident CD8+ T cells up-regulate LFA-1 compared to effector-memory cells, presumably to facilitate this behavior. Finally, we found that LFA-1 deficient CD8+ T cells failed to form substantial liver-resident memory populations following Plasmodium or LCMV immunization. Collectively, our results demonstrate that it is adhesion through LFA-1 that allows liver-resident memory CD8+ T cells to patrol and remain in the hepatic sinusoids.

Isolation of a highly active photosystem II preparation from Synechocystis 6803 using a histidine-tagged mutant of CP 47.

Site-directed mutagenesis was used to produce a Synechocystis mutant containing a histidine tag at the C terminus of the CP 47 protein of Photosystem II. This mutant cell line, designated HT-3, exhibited slightly above normal rates of oxygen evolution and appeared to accumulate somewhat more Photosystem II reaction centers than a control strain. A rapidly isolatable (<7 h) oxygen-evolving Photosystem II preparation was prepared from HT-3 using dodecyl-beta-d-maltoside solubilization and Co2+ metal affinity chromatography. This histidine-tagged Photosystem II preparation stably evolved oxygen at a high rate (2440 micromol O2 (mg chl)-1 h-1), exhibited an alpha-band absorption maximum at 674 nm, and was highly enriched in a number of Photosystem II components including cytochrome c550. Fluorescence yield analysis using water or hydroxylamine as an electron donor to the Photosystem II preparation indicated that virtually all of the Photosystem II reaction centers were capable of evolving oxygen. Proteins associated with Photosystem II were highly enriched in this preparation. 3,3',5, 5'-Tetramethylbenzidine staining indicated that the histidine-tagged preparation was enriched in cytochromes c550 and b559 and depleted of cytochrome f. This result was confirmed by optical difference spectroscopy. This histidine-tagged Photosystem II preparation may be very useful for the isolation of Photosystem II preparations from mutants containing lesions in other Photosystem II proteins.

Cystatin-related epididymal spermatogenic protein colocalizes with luteinizing hormone-beta protein in mouse anterior pituitary gonadotropes.

The CRES (cystatin-related epididymal spermatogenic) protein, a member of the cystatin superfamily of cysteine protease inhibitors, exhibits highly restricted expression in the mouse testis and epididymis, suggesting roles in reproduction. Considering the well-established relationship that exists between the gonads and the neuroendocrine system, the present studies were undertaken to determine whether the CRES messenger RNA and protein are expressed in the anterior pituitary gland and, if so, whether the expression is regulated by hormones. RT-PCR analysis of whole pituitary gland RNA preparations, and Northern blot analyses of pituitary gland cell lines, demonstrated that the CRES gene is expressed in the male and female anterior pituitary gland gonadotropes. Furthermore, Western blot analysis demonstrated that CRES protein was present in whole mouse pituitary glands and was synthesized and secreted by the LbetaT2 gonadotrope cell line. Interestingly, whereas the predominant CRES proteins present in epididymal lysates, LbetaT2 secretory granules, and whole pituitary gland lysates were 19 and 14 kDa, the predominant CRES proteins present in the cell culture conditioned media were 17 and 12 kDa. Deglycosylation studies revealed that the higher-molecular-mass CRES proteins (19 and 17 kDa) were the result of N-linked glycosylation, caused by the presence of high mannose residues. Double-label immunofluorescence and confocal microscopic analysis of male and female mouse pituitary gland tissue confirmed the RNA studies and showed that CRES protein colocalized with LHbeta protein in the gonadotropes. Finally, gonadectomy and hormone replacement studies suggest that CRES protein in the gonadotropes is hormonally regulated. These studies suggest that CRES protein may perform a role in the gonadotrope-mediated control of reproduction.

Perspectives on combination chemotherapy with concomitant radiotherapy for poor-prognosis head and neck cancer.

Concomitant chemoradiotherapy has resulted in small increases in disease-free or overall survival for patients with advanced head and neck cancer when single-agent chemotherapy is used. To increase the efficacy of this approach, combination chemotherapy also has been explored. In this setting, acute toxicities are frequently increased, necessitating interruption or protraction of radiotherapy. Despite this fact, pilot trials using 5-fluorouracil-based chemotherapy have indicated high response and encouraging survival rates. Some of these trials will be reviewed, with a focus on studies with 5-fluorouracil, hydroxyurea, and cisplatin conducted at the University of Chicago.

Practical applications of Beam's Eye View-based treatment planning to head and neck sites.

Because of the complex anatomy of the structures involved by tumor as well as of the critical normal structures, treatment planning for advanced or spatially irregular cancers of head and neck sites is often extremely challenging. Computerized axial tomographic scanning is frequently invaluable in delineating tumor extension into areas inaccessible to physical examination. Our Beam's Eye View Planning (BEVP) capability allows us to incorporate this radiographic information accurately into actual plans used in the clinic. Over the past 2 1/2 years, we have applied this technique to 31 selected head and neck cancer patients at Michael Reese/University of Chicago Center for Radiation Therapy. Tumors were chosen on the basis of anatomical complexity: most involved multiple head and neck sites including orbit, skull base, paranasal sinuses and cavernous sinus. In all cases, radiation tolerance of critical normal structures including spinal cord, brain stem, optic chiasm, and eye had to be considered. With careful use of rigid immobilization devices and the outlining of several normal structures for purposes of alignment, we had no difficulty applying our BEVP technique to clinical simulations. Oblique field blocking was especially facilitated by BEVP. We found the BEVP technique very useful to assure that tumor coverage was adequate and tolerance of normal tissues not exceeded.

Photon neutron mixed-beam radiotherapy of locally advanced prostate cancer.

PURPOSE: In this article we present the results of mixed-beam, photon/neutron radiation therapy in 45 patients with locally advanced, bulky, or postoperative recurrent prostate cancer treated at the University of Chicago between 1978 and 1991. Survival, disease-free survival, local control, and long-term complications are analyzed in detail. METHODS AND MATERIALS: Between 1978 and 1991, 45 patients with locally advanced (> 5 cm State B2, Stage C, or Stage D1) prostate cancer underwent mixed-beam (photon/neutron) radiation therapy. Forty percent of the treatment was delivered with neutron irradiation at either the University of Chicago or Fermilab. Sixty percent of treatment was delivered with photons at the University of Chicago. Initially, the whole pelvis was irradiated to 50 photon Gy equivalent. This was followed by a boost to the prostate for an additional 20 photon Gy equivalent. RESULTS: The median follow-up for patients in this series is 72 months. The overall 5-year actuarial survival was 72%, and the 5-year disease-free survival was 45%. Thus far, 18 patients have died. Eleven patients have died from prostate cancer and 7 from other medical illness. Twenty-seven patients are alive, and 12 of these patients have recurrent and or metastatic disease. The local control rate was 89% (40 out of 45). Histologic material was available on 18 patients following treatment (i.e., prostate biopsy in 16 patients and autopsy in 2 patients) and was negative for carcinoma in 13 (72%). Significant Grade 3-5 complications occurred in 36% (16 out of 45) of the patients treated with mixed-beam radiation therapy and were related to dose and beam quality. Factors related to survival, disease-free survival, local control, and complications are analyzed. CONCLUSIONS: The survival and local control results of mixed-beam radiation therapy at the University of Chicago appear to be superior to those series using photon radiation in patients with locally advanced prostate carcinoma. Mixed-beam radiation therapy should remain an alternative to studies using dose escalation or implant techniques as a method to increase local control and survival at institutions with this capability. However, appropriate plans with high-energy neutrons are necessary to minimize complications.

Effect of subcutaneous recombinant human erythropoietin in cancer patients receiving radiotherapy: preliminary results of a randomized, open-labeled, phase II trial.

PURPOSE: To determine the efficacy and safety of subcutaneous administration of recombinant human erythropoietin (r-HuEPO) at a dose of 200 units/kg/day to cancer patients undergoing radiotherapy. METHODS AND MATERIALS: This is a randomized, open-labeled, Phase II study. Only patients receiving radiotherapy +/- chemotherapy are included. Eligibility is restricted to patients with lung cancer, carcinoma of the uterine cervix, prostatic adenocarcinoma, or adenocarcinoma of the breast. Patients in the control and treatment arms receive radiotherapy with similar policies, and their doses of radiotherapy and treatment volumes are determined by the site and stage of the disease. Patients in the "treatment arm" receive 200 units/kg/day of r-HuEPO, subcutaneously, five times a week with iron (Fe SO4, 325 mg. p.o., t.i.d.) supplements. Complete blood counts are obtained weekly. Quality of life is assessed weekly by the patients themselves by a few simple entries on an analog scale. RESULTS: Twenty-six patients have been entered in the study so far. Twelve patients were placed in the control arm and 14 in the treatment arm. Pre-randomization demographic and laboratory mean values in both arms were comparable, with none of 16 parameters compared reaching statistical significance. Our results can be summarized as follows: (a) Mean hemoglobin, hematocrit, and red blood cell values increased gradually in the treatment arm patients. Week-by-week comparison showed that mean values for these three parameters were significantly higher in the treatment arm than in the control arm. For example, the p values for the differences in hemoglobin mean values for weeks 1-6 were 0.015, 0.002, 0.003, 0.0002, 0.0006, and 0.007, respectively. Similar trends were observed for red blood cells and the hematocrit values. (b) No significant toxicity has been encountered. (c) No significant differences in the mean values of white blood cells and platelet counts were seen between the two arms. The values of these two parameters declined over the course of radiotherapy. (d) The mean weekly increase in hemoglobin levels in the treatment arm was 0.43 gm/dl. CONCLUSION: (a) The safety and efficacy of r-HuEPO, with 200 units/kg/day of subcutaneous administration, have been confirmed in our study group. (b) However, the rate of increase in hemoglobin levels is not very rapid with the doses used. (c) Dose escalation studies are needed for determination of the feasibility of improving hemoglobin levels by about 1 gm/dl/week. (d) The question whether improvement in hemoglobin with r-HuEPO therapy can improve outcome by improving tumor oxygenation needs to be studied in carcinoma of the uterine cervix and squamous cell carcinoma of the head and neck.

Analysis of weekly complete blood counts in patients receiving standard fractionated partial body radiation therapy.

PURPOSE: Hematopoiesis is among the most sensitive systems in the body to radiation. Routine complete blood counts (CBCs) are common in clinical radiotherapy practice. Only a few studies have attempted to characterize the behavior of peripheral blood levels during partial body radiation therapy with field sizes smaller than those used in hemibody or total nodal irradiation. Such information is needed to identify which patients are at risk for cytopenia and require close monitoring. METHODS AND MATERIALS: In 1993, 412 new patients were seen at Michael Reese Hospital for radiotherapy. A total of 972 weekly CBCs were identified for 155 patients receiving a minimum of 5 weeks of treatment for breast, prostate, lung, gynecological, or head and neck malignancies. Linear regression models were fitted to the weekly CBC values for those patients who had pretreatment CBC values recorded. Factors affecting starting levels, rates of decline, and nadirs during treatment were determined for leukocytes, platelets, and hemoglobin. RESULTS: Leukocytes declined most dramatically during the first week of treatment (16% from pretreatment to Week 1 levels) and then at a rate of 3.3% per week from Week 1 to Week 7 (p < 0.001). Total mean leukocyte decrease over 7 weeks of therapy was 30%. Platelets declined 9% on average during the first week of therapy and then at a mean rate of 1.4% per week (p < 0.02). A statistically significant decrease in hemoglobin levels could not be detected. No difference in the rate of decrease could be found for different disease sites, age groups, or amount of marrow irradiated. The effects of chemotherapy were variable, depending on blood element and whether therapy was sequential or concomitant. The odds of a nadir < 2000 counts/mm3 for white blood count (WBC), < 50,000 counts/mm3 for platelets, and < 8.0 g/dl for hemoglobin were all well below 5%. A strong correlation existed between starting CBC values and nadirs; patients with lower Week 1 CBC levels were most likely to have the lowest nadirs. CONCLUSIONS: Low CBC levels during radiation therapy are likely to be the result of other medical problems that cancer patients face. Regional irradiation with small field sizes (< 40% of total body marrow) typically used in clinical radiotherapy is unlikely to be the cause of marrow depression significant enough to warrant medical intervention. Blood levels taken during the first week of treatment (Week 1) can be used to determine risks of developing critical nadirs. Localized breast and prostate cancer patients are unlikely to require routine CBCs if initial levels are normal. Routine CBC levels on all radiation oncology patients without other reasons for hematopoietic depression requires reevaluation, as millions of dollars are spent on unnecessary testing. If weekly CBC blood levels are avoided in localized breast and prostate cancer patients, this alone could potentially result in a savings of as much as $40 million a year nationally.

Late rectal sequelae following definitive radiation therapy for carcinoma of the uterine cervix: a dosimetric analysis.

PURPOSE: This study attempted to correlate patient, treatment, and dosimetric factors with the risk of late rectal sequelae in patients treated with radiation therapy (RT) for cervical carcinoma. METHODS AND MATERIALS: A total of 183 patients with cervical carcinoma (67 Stage I, 93 Stage II, and 23 Stage III) treated with definitive RT with a minimum of 2 years follow-up were evaluated. Treatment consisted of external beam pelvic RT (EBRT) followed by intracavitary RT (ICRT) consisting of one or two insertions. Complications were scored and analyzed as a function of 25 patient and treatment factors. Conventional total rectal doses were obtained by adding together the EBRT and ICRT rectal doses. To account for differences in dose rate between the ICRT and EBRT, and variations in EBRT fractionation schemes, biologically equivalent rectal doses (BED) were calculated using a linear quadratic model. In addition, the influence of the varying proportions of EBRT and ICRT rectal doses were evaluated. RESULTS: Twenty-eight patients (15.3%) developed late rectal sequelae (13 Grade 1, 3 Grade 2, and 12 Grade 3). Diabetes (p = 0.03), Point A dose (p = 0.04), and conventional EBRT dose (p = 0.03) were the most significant factors on multivariate analysis. Logistic regression analysis demonstrated a low risk (<10%) of late rectal sequelae below conventional and biological rectal doses of 75 Gy and 135 BED, respectively. The percentage of rectal dose delivered by the EBRT significantly influenced the dose-response relationship. A defined threshold percentage above which rectal sequelae were more common was identified over the range of doses evaluated. This threshold was 87% at a total rectal dose of 60 Gy and decreased to 60% at 80 Gy. CONCLUSION: Diabetes, Point A, and EBRT doses are the most significant factors associated with the risk of late rectal sequelae in patients treated with RT for cervical carcinoma. The percentage of rectal dose delivered by the EBRT significantly affects the conventional and biological dose-response relationship. This suggests that the volume of rectum irradiated is an important and independent parameter in the development of late rectal sequelae.

Auto-oxidation of dialuric acid, divicine and isouramil. Superoxide dependent and independent mechanisms.

The toxicity of dialuric acid to pancreatic beta cells, and the haemolytic action of divicine and isouramil involve auto-oxidation and redox cycling reactions. Divicine and isouramil are produced on hydrolysis of the fava bean glycosides, vicine and convicine. The mechanism of auto-oxidation of the three compounds as well as the acid hydrolysis product of vicine (provisionally assigned the structure 2-amino-4,5,6-trihydroxypyrimidine) has been studied. All four pyrimidines auto-oxidized rapidly at neutral pH, generating H2O2 by an O2-dependent chain mechanism. Superoxide dismutase inhibited the initial oxidation, but inhibition was transitory, and after a lag period rapid oxidation occurred. The lag period varied with pH, temperature and pyrimidine concentration, and was much shorter for isouramil and divicine than for dialuric acid and acid-hydrolysed vicine. The initial rate of dialuric acid oxidation was greater and the acceleration less pronounced than with the other pyrimidines. A mechanism common to all four pyrimidines has been shown by kinetic analysis to account for nearly all the observations in the presence and absence of superoxide dismutase. Autocatalysis in the latter case is attributed mainly to the reactions reduced pyrimidine + oxidized pyrimidine in equilibrium 2 pyrimidine radical pyrimidine radical + O2----oxidized pyrimidine + O2- Rate constants for these and other reactions are reported. At pH 7.4 and 37 degrees the lag period before 100 microM acid-hydrolysed vicine underwent rapid oxidation was approx. 15 min. Isouramil and divicine at an equivalent concentration gave lags of less than 1 min, which became less at higher concentrations. Thus intracellular superoxide dismutase should provide only transitory protection against the oxidation products of dialuric acid, divicine or isouramil. Prolonged protection should only be achieved if accumulation of oxidized pyrimidine is also prevented.

Acquired syphilitic uveitis.

Secondary syphilis is an overlooked cause of iritis and posterior uveitis. Three cases of acquired syphilitic uveitis were observed, two of which occurred in male homosexuals. In the first patient, a delay in diagnosis and treatment led to irreversible loss of vision and visual field. In the latter two cases, an increased index of suspicion led to earlier diagnosis and treatment, with complete recovery of vision.

Effect of external beam radiation therapy on serum prostate-specific antigen.

The effect of external beam radiation on serum prostate-specific antigen (PSA) was determined in 20 patients with nonmetastatic carcinoma of the prostate. An abnormal PSA was measured in 91 percent and 93 percent, respectively, of the samples collected prior to or during radiation therapy. By seven months, 8/15 men still had an abnormal PSA level. Four of 5 men with an elevated PSA at least twenty-three months after radiation therapy had a positive prostatic biopsy, and 3/3 patients with a normal PSA had a negative ultrasonically guided biopsy. The rate of decline of serum PSA after radiation therapy is variable. These preliminary data suggest that serum PSA may be useful for assessing the local response of prostate cancer to radiation therapy.

Sandwich radiotherapy (3,000 and 4,500 rads) around radical retropubic prostatectomy for stage C prostatic carcinoma.

Supervoltage external radiotherapy has been sandwiched around radical retropubic prostatectomy as a potentially curative procedure for Stage C or D1 adenocarcinoma of the prostate. Preoperatively, 3,000 rads were delivered to the pelvis and prostate by approximately 18 by 20 cm. AP-PA opposing ports over a three-week period. After three weeks' rest, radical retropubic prostatectomy was done. After three weeks' postoperative recovery, additional radiotherapy was delivered as follows: 2,000 rads to the pelvis and prostatic fossa by AP-PA opposing ports, plus 2,500 rads to the prostatic fossa alone by 360 degree rotation, plus 4,500 rads to the abdominal periaortic-caval lymph node area. Fifteen cases have been followed for up to five and one-half years to date without serious complications of the therapy and without demonstrable recurrent or residual tumor in the pelvis.

Computer-aided geometric reconstruction of Fletcher-Suit source positions.

A computer-aided method for reconstruction of the source positions of a Fletcher-Suit applicator has been developed. The tandem source positions are determined by digitizing of the tip and two arbitrary points on the shaft from each of two orthogonal simulator films. A colpostat source position is reconstructed by digitizing of a single point on the endcap and three arbitrary points on the cylindrical sidewalls of the colpostat on the films. This computer-aided method considers the true projection geometry and applicator shape and permits localization of the source positions to within a mean error of less than 1 mm. Compared with the conventional method, the new approach (1) is more time efficient because only a few easily identified points are digitized, (2) allows localization when the tandem sources are shifted by a spacer or when colpostat sources are difficult to visualize on the lateral film, and (3) is more accurate than the conventional technique because no manual drawing of source positions on films is involved.

Corneal topography following excimer photorefractive keratectomy for myopia.

Corneal topographic analysis was performed on 97 consecutive eyes with at least one month follow-up after excimer laser photorefractive keratectomy for myopia. Centration of the ablated zone was documented in all eyes at the one month postoperative examination with the Topographic Modeling System (Computed Anatomy Inc., NY). Thirty-seven percent of eyes were within 0.25 mm of the pupillary center (PC); 48% of eyes were between 0.25 and 0.50 mm, 13% were between 0.50 and 1.00 mm, and 2% were more than 1.00 mm from the PC. The greatest amount of decentration was 1.50 mm. The mean decentration was 0.36 mm. The surface regularity index (SRI), which is a measure of the optical performance of the cornea, was significantly less at the sixth postoperative month than at the first postoperative month (P = .013). No correlation between the SRI and the amount of decentration was found. Four main patterns of ablation were noted by differential topographic analysis at the one month interval. A central uniform ablation was present in 45% of eyes; "semicircular ablations" were present in 33% of eyes, a "keyhole" ablation pattern in 12%, and a curious "central bump" ablation pattern in 10%. Corneal topographic analysis was a useful tool for documenting and quantitating results following excimer photorefractive surgery.

Accuracy of Orbscan total optical power maps in detecting refractive change after myopic laser in situ keratomileusis.

PURPOSE: To determine whether the refractive change obtained using the Orbscan-derived total optical power (TOP) map is in concordance with the manifest refractive change produced by laser in situ keratomileusis (LASIK). SETTING: LASIK Vision Canada, Vancouver, BC, Canada (an ambulatory surgical center for refractive surgery). METHODS: Twenty eyes of 10 consecutive bilateral LASIK patients were included in the study. Orbscan topographical analysis and manifest refraction were performed preoperatively and at least 1 month postoperatively. The change in manifest refraction (corrected to the corneal plane) before and after LASIK was correlated with the corneal power change averaged within the 2.0, 3.0, 4.0, and 5.0 mm diameter zones of TOP and axial power maps. RESULTS: The central 4.0 mm zone TOP map gave the best correlation between manifest refractive change and Orbscan-measured corneal power change (r2 = 0.835, P < .004). The correlation was higher with TOP maps than with anterior axial power maps. CONCLUSION: The corneal power change measured by the Orbscan TOP maps correlated highly with the changes in manifest refraction after LASIK.

The impact of induced mutations on human populations.

The major impact of an increase in genetic damage will be expressed as an increase in autosomal dominant and X-linked traits as well as chromosomal disorders. The present incidence of dominant traits has been estimated at 1% of live births, but recent data from British Columbia indicate the true value in that population may be an order of magnitude lower. These estimates are important if one measures the damage in terms of doubling dose. Neither the average mutation rate nor the number of loci capable of mutating to dominant detrimental form is known. Mutations that cause sterility or early embryonic loss are detrimental in the Darwinian sense but have little impact on society. Mutations that are more fit biologically may be a heavy burden to society if the affected persons require medical or institutional care. Since exposure to some mutagens is unavoidable, these factors must ultimately be included in a cost-benefit analysis.