Pharmacological activation of the Sonic hedgehog pathway with a Smoothened small molecule agonist ameliorates the severity of alcohol-induced morphological and behavioral birth defects in a zebrafish model of fetal alcohol spectrum disorder.

Ethanol exposure during the early stages of embryonic development can lead to a range of morphological and behavioral differences termed fetal alcohol spectrum disorders (FASDs). In a zebrafish model, we have shown that acute ethanol exposure at 8-10 hr postfertilization (hpf), a critical time of development, produces birth defects similar to those clinically characterized in FASD. Dysregulation of the Sonic hedgehog (Shh) pathway has been implicated as a molecular basis for many of the birth defects caused by prenatal alcohol exposure. We observed in zebrafish embryos that shh expression was significantly decreased by ethanol exposure at 8-10 hpf, while smo expression was much less affected. Treatment of zebrafish embryos with SAG or purmorphamine, small molecule Smoothened agonists that activate Shh signaling, ameliorated the severity of ethanol-induced developmental malformations including altered eye size and midline brain development. Furthermore, this rescue effect of Smo activation was dose dependent and occurred primarily when treatment was given after ethanol exposure. Markers of Shh signaling (gli1/2) and eye development (pax6a) were restored in embryos treated with SAG post-ethanol exposure. Since embryonic ethanol exposure has been shown to produce later-life neurobehavioral impairments, juvenile zebrafish were examined in the novel tank diving test. Our results further demonstrated that in zebrafish embryos exposed to ethanol, SAG treatment was able to mitigate long-term neurodevelopmental impairments related to anxiety and risk-taking behavior. Our results indicate that pharmacological activation of the Shh pathway at specific developmental timing markedly diminishes the severity of alcohol-induced birth defects.

The effect of 2 different premilking stimulation regimens, with and without manual forestripping, on teat tissue condition and milking performance in Holstein dairy cows milked 3 times daily.

The objectives were to study the effect of 2 different premilking stimulation regimens, with and without manual forestripping, on teat tissue condition and milking characteristics in dairy cows. In a randomized controlled crossover study, 130 Holstein cows milked 3 times daily were assigned to treatment and control groups. Premilking udder preparation for the treatment group consisted of: (1) predipping with 1% iodine, (2) sequential forestripping of 3 streams of milk per quarter, (3) wiping of teats, and (4) attachment of the milking unit. Premilking udder preparation for the control group was identical except that the forestripping step was omitted. The mean tactile stimulation durations were 16 s and 7 s for the treatment and control group, respectively. The time spent from first tactile stimulus (either forestripping or wiping of teats) to milking unit attachment was kept consistent at 90 s for both groups. The study lasted for 14 d with 2 periods, each consisting of a 2-d adjustment time followed by 5 d of data collection. Machine milking-induced short-term changes to the teat tissue were assessed by palpation and visually. The following milking characteristics were assessed with electronic on-farm milk meters: milk yield (MY), milking unit-on time (MUOT), 2-min MY (2MIN), and time spent in low milk flow rate (LMF). Generalized linear mixed models were used to describe the effect of treatment on the outcome variables. The odds of machine milking-induced short-term changes to the teat tissue were lower for cows that received forestripping compared with cows that were not forestripped (odds ratio = 0.31; 95% confidence interval = 0.22-0.42). Least squares means (95% confidence interval) for cows that were forestripped and animals that were not forestripped, respectively, were 12.7 (12.2-13.2) and 12.7 (12.2-13.2) kg for MY and 6.1 (5.8-6.4) and 5.6 (5.3-5.9) kg for 2MIN. There was an interaction between treatment and MY for LMF. Time spent in LMF for cows that were forestripped and received no forestripping, respectively, were 18 (17-20) and 24 (23-26) s for a MY level of 10 kg; and 13 (12-14) and 15 (14-16) s for a MY level of 15 kg. The effect of treatment on MUOT was modified by parity. Milking unit-on times for animals in first, second and third or greater lactation, respectively, were 230 (219-243), 249 (236-262), and 260 (249-272) s for cows that were forestripped, and 245 (232-258), 252 (239-266), and 268 (257-281) s for cows that received no forestripping. In this study, cows that were forestripped had shorter MUOT, higher 2MIN, lower LMF, and lower odds of exhibiting changes to the teat tissue after machine milking. We conclude that wiping of teats during premilking udder preparation alone and omitting forestripping of teats without compensating for the loss in stimulation time may not provide sufficient tactile stimulation to elicit the cows' maximum physiological milk-ejection capacity. This can aggravate the adverse effects of vacuum-induced forces on teat tissue during machine milking, diminish animal well-being, and possibly affect udder health.

Chimeric rabies SADB19-VSVg-pseudotyped lentiviral vectors mediate long-range retrograde transduction from the mouse spinal cord.

Lentiviral vectors have proved an effective method to deliver transgenes into the brain; however, they are often hampered by a lack of spread from the site of injection. Modifying the viral envelope with a portion of a rabies envelope glycoprotein can enhance spread in the brain by using long-range axon projections to facilitate retrograde transport. In this study, we generated two chimeric envelopes containing the extra-virion and transmembrane domain of rabies SADB19 or CVS-N2c with the intra-virion domain of vesicular stomatitis virus. Viral particles were packaged containing a green fluorescent protein reporter construct under the control of the phosphoglycerokinase promoter. Both vectors produced high-titer particles with successful integration of the glycoproteins into the particle envelope and significant transduction of neurons in vitro. Injection of the SADB19 chimeric viral vector into the lumbar spinal cord of adult mice mediated a strong preference for gene transfer to local neurons and axonal terminals, with retrograde transport to neurons in the brainstem, hypothalamus and cerebral cortex. Development of this vector provides a useful means to reliably target select populations of neurons by retrograde targeting.

Circulating biomarkers for detection of ovarian cancer and predicting cancer outcomes.

BACKGROUND: Securing a diagnosis of ovarian cancer and establishing means to predict outcomes to therapeutics remain formidable clinical challenges. Early diagnosis is particularly important since survival rates are markedly improved if tumour is detected early. METHODS: Comprehensive miRNA profiles were generated on presurgical plasma samples from 42 women with confirmed serous epithelial ovarian cancer, 36 women diagnosed with a benign neoplasm, and 23 comparably age-matched women with no known pelvic mass. RESULTS: Twenty-two miRNAs were differentially expressed between healthy controls and the ovarian cancer group (P<0.05), while a six miRNA profile subset distinguished presurgical plasma from benign and ovarian cancer patients. There were also significant differences in miRNA profiles in presurgical plasma from women diagnosed with ovarian cancer who had short overall survival when compared to women with long overall survival (P<0.05). CONCLUSION: Our preliminary data support the utility of circulating plasma miRNAs to distinguish women with ovarian cancer from those with a benign mass and identify women likely to benefit from currently available treatment for serous epithelial ovarian cancer from those who may not.

Colour compatibility between teeth and dental shade guides in Quinquagenarians and Septuagenarians.

The aim of this investigation was to determine colour compatibility between dental shade guides, namely, VITA Classical (VC) and VITA 3D-Master (3D), and human teeth in quinquagenarians and septuagenarians. Tooth colour, described in terms of L*a*b* values of the middle third of facial tooth surface of 1391 teeth, was measured using VITA Easyshade in 195 subjects (48% female). These were compared with the colours (L*a*b* values) of the shade tabs of VC and 3D. The mean coverage error and the percentage of tooth colours being within a given colour difference (DeltaE(ab)) from the tabs of VC and 3D were calculated. For comparison, hypothetical, optimized, population-specific shade guides were additionally calculated based on discrete optimization techniques for optimizing coverage. Mean coverage error was DeltaE(ab) = 3.51 for VC and DeltaE(ab) = 2.96 for 3D. Coverage of tooth colours by the tabs of VC and 3D within DeltaE(ab) = 2 was 23% and 24%, respectively, (DeltaE(ab)

Iodinated contrast media: effect of osmolarity and injection temperature on erythrocyte morphology in vitro.

BACKGROUND: Some side effects of intravenously injected iodinated contrast media are thought to be linked to the biological properties of the various agents and their effect on blood components. PURPOSE: To assess the effect of osmolarity and injection temperature of iodinated contrast media on erythrocyte (RBC) morphology in vitro. MATERIAL AND METHODS: Blood from 20 volunteers was incubated with three different contrast media (320 mg I/ml iso-osmolar iodixanol, 300 mg I/ml low-osmolar iopromide, 300 mg I/ml low-osmolar iopamidol) injected at 37 degrees C, 43 degrees C, and 48 degrees C, and in two different volumes corresponding to the estimated concentration at the site of venous injection and after systemic distribution. After 10 min incubation, aliquots were removed for complete blood count analysis and blood smears. Two hematologists blindedly and independently reviewed all smears, and determined the grade of morphological RBC changes compared to a blank sample. RESULTS: There was excellent (kappa = 0.98) inter-reader correlation for grading RBC changes. At systemic concentration at 37 degrees C, the grade of RBC changes was significantly (P<0.05) less in blood samples exposed to iso-osmolar iodixanol (mean 0.21) as compared to low-osmolar iopromide (mean 0.26) and low-osmolar iopamidol (mean 0.58). These differences became more significant at higher volumes, corresponding to concentrations at the site of injection and higher injection temperatures. CONCLUSION: In vitro, RBC morphology is less affected by iso-osmolar as compared to low-osmolar contrast media. These differences become more significant at higher injection temperatures that are proposed to improve flow dynamics for high-speed injection.

[SaO2 and PaO2 mismatch: Do not forget hemoglobinopathy]. / Discordance entre SaO2 ­ PaO2 : ne pas oublier les hémoglobinopathies.

INTRODUCTION: Different clinico-biological parameters are used to estimate the amount of oxygen available for the organism. Oxygen saturation measured with pulse oxymetry (SpO2), oxygen saturation of arterial blood (SaO2) and oxygen partial pressure of the arterial blood (PaO2) are the most commonly used. CASE REPORT: We report the case of a patient admitted for investigation of respiratory failure in the context of chronic dyspnea of effort. SpO2 and SaO2 were decreased, though the PaO2 was normal. This mismatch between oxygen saturation and PaO2 led to the diagnosis of hemoglobinopathy (Bassett hemoglobin). CONCLUSION: The diagnosis of hemoglobinopathy should be considered in cases of oxygen desaturation with normal respiratory and cardiac investigations. There are no reasons to prescribe long-term oxygen to these patients.

Polymorphism of Alprazolam (Xanax): a review of its crystalline phases and identification, crystallographic characterization, and crystal structure of a new polymorph (form III).

A new polymorphic form of Alprazolam (Xanax), 8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo-[4,3-alpha][1,4]benzodiazepine, C(17)H(13)ClN(4), has been investigated by means of X-ray powder diffraction (XRPD), single crystal X-ray diffraction, and differential scanning calorimetry (DSC). This polymorphic form (form III) was obtained during DSC experiments after the exothermic recrystallization of the melt of form I. The crystal unit cell dimensions for form III were determined from diffractometer methods. The monoclinic unit cell found for this polymorph using XRPD after indexing the powder diffractogram was confirmed by the cell parameters obtained from single crystal X-ray diffractometry on a crystal isolated from the DSC pans. The single crystal unit cell parameters are: a = 28.929(9), b = 13.844(8), c = 7.361(3) angstroms, beta = 92.82(3) degrees , V = 2944(2) angstroms(3), Z = 8, space group P2(1) (No.4), Dx = 1.393 Mg/m(3). The structure obtained from single crystal X-ray diffraction was used as initial model for Rietveld refinement on the powder diffraction data of form III. The temperature phase transformations of alprazolam were also studied using high temperature XRPD. A review of the different phases available in the Powder Diffraction File (PDF) database for this drug is described bringing some clarification and corrections.

Crystal structure of carnidazole form II from synchrotron X-ray powder diffraction: structural comparison with form I, the hydrated form and the low energy conformations in vacuo.

The crystal structure of carnidazole form II, O-methyl [2-(2-methyl-5-nitro-1H-imidazole-1-yl)ethyl]thiocarbamate, has been determined using synchrotron X-ray powder diffraction in combination with simulated annealing and whole profile pattern matching, and refined by the Rietveld method. For structure solution, 12 degrees of freedom were defined: one motion group and six torsions. Form II crystallizes in space group P2(1)/n, Z=4, with unit cell parameters after Rietveld refinement: a=13.915(4), b=8.095(2), c=10.649(3) A, beta=110.83(1) degrees, and V=1121.1(5) A3. The two polymorphic forms, as well as the hydrate, crystallize in the monoclinic space group P2(1)/n having four molecules in the cell. In form II, the molecules are held together by forming two infinite zig-zag chains via hydrogen bonds of the type N--H...N, the same pattern as in form I. A conformational study of carnidazole, at semiempirical PM3 level, was performed using stochastic approaches based on modification of the flexible torsion angles. The values of the torsion angles for the molecules of the two polymorphic forms and the hydrate of carnidazole are compared to those obtained from the conformational search. Form I and form II are enantiotropic polymorphic pairs this agrees with the fact that the two forms are conformational polymorphs.

[Intravascular optical coherence tomography: differentiation of atherosclerotic plaques and quantification of vessel dimensions in crural arterial specimens]. / Intravaskuläre optische Kohärenztomographie: Unterscheidung verschiedener Plaquetypen und Vermessung von Gefässdimensionen in atherosklerotischen Unterschenkelarterien.

PURPOSE: Intravascular optical coherence tomography (OCT) is a new technique based on infrared light that visualizes the arteries with a resolution of 10-20 microm. Intravascular ultrasound (IVUS) is the current in vivo reference standard and provides a resolution of 100-150 microm. This study compared OCT to IVUS and histopathology with respect to the ability to differentiate atherosclerotic plaques and quantify vascular dimensions in peripheral crural arteries ex vivo. MATERIALS AND METHODS: 50 segments of atherosclerotic arteries derived from five amputated human lower extremities were examined. The different plaque types (fibrous, high-lipid content, calcified) were assigned by two independent examiners, and the sensitivity and specificity of OCT in comparison with histopathology as well as intra- and interobserver consensus were calculated. A comparison of OCT with IVUS addressed the parameters: luminal area (LA), vascular wall area (VA) and plaque area (PA). RESULTS: When comparing OCT and histopathology with respect to the differentiation of various plaque types, sensitivities of 81 % and specificities of 89 % for fibrous plaques, of 100 % and 93 % for lipid-rich plaques and of 80 % and 89 % for calcified plaques were achieved (overall correlation 83 %). Intra- and interobserver consensus was very high (kappa = 0.86 and kappa = 0.89, p < 0.001, respectively). There was also a high correlation between quantitative measurements (Bland-Altman plot [LA]: mean bias, 0.1 mm(2) accuracy +/- 1.8 mm(2), r = 0.95 [p < 0.001] Bland-Altman plot [VA]: mean bias, 0.3 mm(2) accuracy +/- 2.3 mm(2), r = 0.94 [p < 0.001] Bland-Altman plot [PA]: mean bias, 0.4 mm(2) accuracy +/- 2.3 mm(2), r = 0.80 [p < 0.01]. CONCLUSION: OCT allows the differentiation of atherosclerotic plaque types in crural arteries with high accuracy compared to histopathology. Quantitative measurements show a high correlation with IVUS, the current reference standard.

Modulation of insulin signal transduction by eutopic overexpression of the receptor-type protein-tyrosine phosphatase LAR.

Protein-tyrosine phosphatases (PTPases) regulate insulin signaling by catalyzing the tyrosine dephosphorylation of the insulin receptor and its substrate proteins. Previous studies have implicated a PTPase localized to a cell membrane fraction in the regulation of the insulin receptor in situ. LAR (leukoyte antigen related) is a transmembrane PTPase in insulin-sensitive tissues with in vitro catalytic specificity for the insulin receptor kinase domain. When transfected into Chinese hamster ovary cells overexpressing the human insulin receptor (CHO-hlR), the LAR protein was processed as expected into an 85-kDa subunit containing the transmembrane and cytoplasmic domains. LAR was increased an average of 6-fold in clonal lines of stably transfected cells, and cell fractionation confirmed its localization in the cell membrane. After stimulation with 100 nM insulin, tyrosine phosphorylation of the insulin receptor was decreased by 31% at 1 min (P < 0.01) and by 42% at 10 min (P < 0.01), and that of IRS-1 was decreased by 34% (P < 0.01) at 1 min and by 56% (P < 0.01) at 10 min in the LAR-overexpressing cells compared with empty vector transfectants. LAR overexpression also blocked insulin-stimulated receptor kinase activation as well as thymidine incorporation into DNA. Quantitatively similar results were obtained in populations of CHO-hlR cells transfected transiently by electroporation. In contrast, overexpression of recombinant LAR cytoplasmic domain, detected as a 72-kDa protein in the cell cytosol, did not significantly affect the insulin-stimulated tyrosine phosphorylation of the insulin receptor or IRS-1 (99% and 93% of control at 10 min, respectively). These studies provide the first evidence that increased expression of LAR has negative regulatory effects at a proximal site in the insulin-signaling pathway. Since this effect occurs only when LAR is eutopically expressed at the cell membrane, these data further suggest that LAR requires a transmembrane localization to directly interact with the insulin receptor in situ.

Fibronectin is a non-viral substrate for the HIV proteinase.

The retrovirus encoded proteinase (PR) is required for the proper maturation of viral particles into infectious virus. The PR had been considered highly substrate specific, cleaving exclusively the viral gag and gag-pol protein precursor. It has recently been reported, however, that cytoskeleton and other cellular filament proteins can be cleaved by the HIV-1 PR. Here we have evidence that a cell-associated protein, the fibronectin (A-chain), is also cleaved in vitro specifically by this PR. The possibility of a cytotoxic role of the PR is conceivable.

Dehydroepiandrosterone sulfate (DHEAS): identification of a carrier protein in human liver and brain.

Dehydroepiandrosterone sulfate (DHEAS) is the major circulating steroid in man. Pharmacologically, it exerts marked neuropsychiatric effects. Since no target receptor has been identified, we investigated whether the organic anion transporting polypeptide (OATP), a multispecific steroid carrier, transports DHEAS. Expression of the human liver OATP in Xenopus laevis oocytes resulted in high-affinity, partially Na+-dependent uptake of [3H]DHEAS (Km: 6.6 micromol/l). DHEAS transport was inhibited by bromosulfophthalein, bile acids, sulfated estrogens and dexamethasone. Northern blot analysis showed widespread expression of OATP in human brain. These data identify OATP as the first known target protein of DHEAS in human liver and brain.

Long-range results for breast cancer patients treated by radical mastectomy and postoperative radiation without adjuvant chemotherapy: an update.

Between 1963 and 1977, 941 patients with carcinoma of the breast received, at the University of Texas M.D. Anderson Cancer Center, peripheral lymphatic irradiation alone or with chest wall irradiation after a radical or modified radical mastectomy. None of the patients received adjuvant chemotherapy. The incidence of patients with histologically involved axillary nodes was 70%. The lymphatics of the apex of the axilla, of the supraclavicular area, and of the internal mammary chain were irradiated in patients with histologically positive axillary nodes and/or in patients with central or inner quadrant primaries regardless of the axillary status. When in 1963 an electron beam became available, chest wall irradiation has been added to the peripheral lymphatics irradiation, primarily when there was a heavy infestation of the axillary nodes. The disease-free survival curves tend to flatten out at 10 years. At 10 and 20 years, the disease-free survival rates are respectively 55% and 50% for all patients, 44% and 40% for all patients with positive nodes, 56% and 48% for the patients with one to three positive nodes, and 33% and 30% for the patients with four or more positive nodes. The comparison of the mortality curves between the general population and the breast cancer patients seems to indicate a cured fraction, since the curves become parallel at 17 years. The highest incidence of failures is between 0 and 5 years, still a significant incidence between 5 and 10 years, but after 10 years the incidence of failures is relatively small.

Time course and incidence of late complications in patients treated with radiation therapy for FIGO stage IB carcinoma of the uterine cervix.

PURPOSE: To determine the time course and incidence of late complications from radiation therapy in patients treated with radiation for FIGO Stage IB carcinoma of the uterine cervix, and to evaluate patient and tumor factors associated with an increased probability of treatment complications. METHODS AND MATERIALS: The medical records of 1784 patients with FIGO Stage IB cervical carcinoma who were treated with initial radiation therapy between 1960 and 1989 were retrospectively reviewed. Follow-up was obtained from clinic visits and correspondence with patients and their physicians. Treatment complications were graded retrospectively. Complication rates were calculated actuarially; patients who died of disease or intercurrent illness without experiencing a major complication were censored at the time of death. There were 1241, 924, 548, and 274 patients followed for more than 5, 10, 15, and 20 years, respectively. RESULTS: Of patients treated for Stage IB cervical carcinoma, 7.7% and 9.3% had experienced major (> or = Grade 3) complications at 3 and 5 years, respectively. After 5 years, there was a small but continuous risk of approximately 0.34% per year, resulting in an overall actuarial risk of having had major complications of 14.4% at 20 years. The risk of developing major urinary tract complications was approximately 0.7% per year for the first 3 years of follow-up, decreasing to about 0.25% per year for at least 25 years. In contrast, the risk of developing rectal complications was about 1% per year during the first 2 years, with a subsequent sharp decline to about 0.06% per year between Years 2 and 25. The risk of fistula formation was approximately doubled in the 234 patients who underwent adjuvant extrafascial hysterectomy (5.3 vs. 2.6% at 20 years; p = 0.04) and in the 111 patients who had pretreatment laparotomy (5.2 vs. 2.9%; p = 0.007). The risk of developing small bowel obstruction was increased in patients who underwent pretreatment laparotomy (14.5 vs. 3.7% at 10 years; p < 0.0001) and in patients who weighed < 120 pounds (8.2 vs. 3.6%; p = 0.004), but was not increased in patients who underwent adjuvant hysterectomy. A significantly greater risk of gastrointestinal complications was observed in black and non-Hispanic white patients than in Hispanic women (p = 0.01), even though there was no difference in the rate of developing urinary tract complications (p = 1.0). There was no correlation between the actuarial risk of developing major complications and the patients' age at the time of treatment, but the cumulative risk was greater for patients who were treated at a young age because these patients were more likely to survive to be exposed to a very long period of risk. CONCLUSIONS: Using techniques described by Fletcher and Delclos, the risk of major complications from aggressive irradiation for Stage IB carcinoma of the cervix is low and does not warrant compromises in the intensity of treatment that might decrease the high cure rates achieved in such patients. The long time course of some late complications also suggests that continued surveillance of survivors, by physicians experienced in the diagnosis and management of the sequelae of the curative radiation treatment of cervical cancer, is important.

Guidelines for radiotherapeutic techniques for cervical metastases from an unknown primary.

Between 1968 and 1980, radiotherapy was part of the treatment of 120 patients with cervical nodes from an unknown primary tumor. Thirteen patients presented with supraclavicular nodes only and 14 presented with massive adenopathy; they are analyzed separately. The remaining 93 patients are analyzed in this report with emphasis on the applied radiotherapeutic techniques. Twenty of the 93 patients received radiation treatment to the neck only, 26 to the naso- and oropharynx and neck, and 47 to the naso-, oro-, and hypopharynx and neck. Fourteen patients subsequently developed a tumor at a primary site or a recurrence of metastases in the neck; in nine patients the disease recurrence was in areas that had not been irradiated. There was an increase in failures above the clavicles in patients who received irradiation to the neck alone. No correlation was found between initial tumor staging and subsequent failure, nor between types of surgical procedures and failure. In 86 of 93 (92.5%) patients there was eventual control of disease above the clavicles; 22 of the 93 patients died of disease, whereas 36 died of other causes. The determinate survival rate for the 93 patients treated with curative intent is 70% at 10 years. Guidelines for selection of techniques based on tumor and patient factors are discussed.

Comparison of surgery and radiation therapy for non-small cell carcinoma of the lung with mediastinal metastasis.

Interest in the potential role of induction chemotherapy for patients with marginally operable non-small cell carcinoma of the lung (NSCCL) led to a retrospective study of surgical resection and radiation therapy, alone or combined with each other and/or chemotherapy. All 169 patients seen at The University of Texas M. D. Anderson Cancer Center from 1980 through 1985 with evidence of NSCCL metastatic to ipsilateral mediastinal lymph nodes but without extrathoracic spread were evaluated (NSM0). All patients had histologic or cytologic confirmation of NSCCL and clinical or pathologic evidence of mediastinal involvement. Nine patients received CHM alone and were excluded. The male:female ratio was 3:1, and 50% were less than 60 years old. Squamous cell carcinoma was reported in 42%, adenocarcinoma in 45%, large-cell carcinoma in 9%, and unclassified carcinoma in 4%. Radiation therapy (RT) was selected for 81 patients (+ CHM in 56%), in 85% because of the extent of tumor involvement and in 15 for medical reasons. Of RT patients, 31% had a Karnofsky performance status (KPS) of less than or equal to 80, 30% had greater than 5% weight loss, and 9% had Stage IIIB disease. Surgical resection (SX) was used in 41 patients (+CHM in 41%), of whom 10% had KPS less than or equal to 80, 17% had greater than 5% weight loss, and 2% had Stage IIIB disease. SX + RT was the treatment for 38 patients (+ CHM in 36%), of whom 13% had KPS less than or equal to 80, 13% had greater than 5% weight loss, and 13% had Stage IIIB disease. The proportions of patients with KPS less than or equal to 80 and weight loss greater than 5% were significantly greater (p less than .01 and p less than .05, respectively) in the RT group than in the other treatment groups. Actuarial survival rates at 2 and 5 years were 24% and 9%, respectively, for RT, 32% and 17% for SX, and 46% and 25% for SX + RT. Overall survival rates for all 160 patients were 30% at 2 years and 14% at 5 years. Prognostic factors that were found to be important were KPS (p = .027) and weight loss (p = .001); age, sex, histology, and Stage IIIa versus IIIB disease were not significantly related to outcome. The results of treatment with SX + RT were significantly better than with RT alone (p = .03); the difference between RT alone and SX alone was not significant (p = .39).(ABSTRACT TRUNCATED AT 400 WORDS)

The role of serum prostatic acid phosphatase in the management of adenocarcinoma of the prostate with radiotherapy.

Between 1974 and 1983, 472 patients with clinically-staged adenocarcinoma of the prostate treated by radiotherapy had baseline and follow-up prostatic acid phosphatase (SPAP) measurements by the enzymatic Roy method. The mean pretreatment SPAP was higher in Stage C (0.65 mIU/ml) than in combined Stages A2/B (0.43 mIU/ml), (p less than 0.05). Likewise, the incidence of elevated SPAP (greater than 0.8 mIU/ml) was also higher in Stage C (12%) than in Stages A2/B (3%), (p less than 0.01). Only 3 of 113 patients in Stages A2/B had an elevated SPAP and all three remain disease-free. In Stage C elevated SPAP was an adverse prognostic factor, and patients with a normal SPAP fared worse if their value was in the upper half of normal (greater than 0.4 mIU/ml) rather than in the lower half (less than or equal to 0.4 mIU/ml). However, in Stage C, tumor grade was found to correlate with initial SPAP, so that the higher the grade, the higher was the mean SPAP and the greater was the incidence of elevated SPAP. When stratified for grade, the prognostic significance of low-normal versus high-normal SPAP in Stage C was lost. An elevated SPAP was, however, an independent adverse prognostic factor for patients with intermediate and high grade tumors. Following radiotherapy, mean SPAP values fell significantly within 1-3 months. For patients with initially normal SPAP, this fall was of no prognostic significance. In 80% of the patients with baseline elevation of SPAP, the values normalized following treatment and the relapse rate in these patients was 51%, which was still higher than the relapse rate of patients with initially normal SPAP (33%) (p less than 0.05) but was lower than the 89% relapse rate in patients whose postradiation SPAP did not normalize (p less than 0.05). Pretreatment SPAP was of independent prognostic significance for only 6% of the study population and therefore has quite limited usefulness in the management of this disease. SPAP decreases following radiotherapy, but this is of prognostic significance only for the small group of patients with elevated pretreatment values.

The influence of tumor size and morphology on the outcome of patients with FIGO stage IB squamous cell carcinoma of the uterine cervix.

PURPOSE: To define the influence of tumor size and morphology on rates of central tumor control (CTC), pelvic tumor control (PTC), and disease-specific survival (DSS) in patients treated with radiotherapy for squamous cell carcinoma of the intact uterine cervix. METHODS AND MATERIALS: Records of 1526 patients treated with radiotherapy for FIGO Stage IB squamous cell carcinoma of the intact uterine cervix between 1960 and 1989 were retrospectively reviewed. The maximum tumor or cervical diameter was determined from clinical descriptions for 1494 patients. Tumors were divided into nine size categories. Tumors > or = 4 cm were further classified according to the dominant morphology (i.e., exophytic or endocervical). Median follow-up was 12.2 years. Five-year CTC, PTC, and DSS rates were calculated actuarially. RESULTS: CTC, PTC, and DSS rates correlated strongly with tumor diameter (p < 0.0001). Overall, CTC, PTC, and DSS rates for patients with tumors < 5 cm were 99%, 97%, and 88%, respectively. For patients with tumors 5-7.9 cm these rates were 93%, 84%, and 69%, respectively. There were no significant differences in the rates of PTC, CTC, or DSS between subgroups of patients with lesions 5-7.9 cm in diameter. The rates of CTC (97%) and DSS (76%) for patients with 5-7.9 cm exophytic tumors were significantly better than those for patients with endocervical tumors of the same size (91% and 66%, respectively); there was no difference in the PTC rate. CONCLUSION: Although the CTC rates were excellent for all patients with tumors < 8 cm in diameter, these rates for tumors < 5 cm (99%) and for exophytic tumors 5-7.9 cm (97%) make it difficult to justify the use of adjuvant hysterectomy. Although patients with tumors of 5-7.9 cm had consistently poorer PTC and DSS rates than did patients with smaller tumors, the control rates achieved with aggressive radiotherapy were still excellent. The strong correlation between tumor size and outcome suggests that tumor diameter should be assessed when tumors are clinically evaluated and staged and when treatment results are reported for patients with FIGO Stage IB carcinoma of the uterine cervix.

Prognostic implications of age in breast cancer patients treated with tumorectomy and irradiation or with mastectomy.

Conservation breast treatment is of particular interest to young women, but whether saving the breast carries a penalty in shorter survival or local-regional recurrent disease has not been well-established. At The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston, 1161 patients treated prior to 1983 with Stage I or II breast cancer were reviewed. Of these patients, 378 were treated with tumorectomy plus irradiation, and 783 were treated with radical or modified radical mastectomy. The two patient groups were compared relative to local-regional disease recurrence and overall and disease-free survivals. Local recurrences in the breast appear to be more frequent in patients less than or equal to 35 years of age treated with tumorectomy and irradiation than in patients older than 35 years, but in patients aged less than or equal to 50 or greater than 50 or less than or equal to 35 or greater than 35 years, there was no significant statistical difference between tumorectomy and irradiation or mastectomy nor was there a difference in disease-free survival. Overall survival rates favored patients treated by tumorectomy and irradiation.