Vesico-appendiceal fistula revealing pseudomyxoma peritonei.

We report a case of grade III pseudomyxoma peritonei revealed by mucusuria and abdominal mass. These symptoms are unusual; the most frequent clinical presentation is acute appendicitis or progressively increasing abdominal diameter.

Circulating levels of inhibin A, inhibin B and activin A in normal and intrauterine growth restricted (IUGR) fetuses.

OBJECTIVE: To evaluate the relationships between circulating levels of inhibin A, inhibin B and activin A, and sex, gestational age and gonadotropins in normal and pathological fetuses. STUDY DESIGN: The study included 31 normal fetuses and 12 affected with intrauterine growth restriction (IUGR) of gestational age ranging 20-40 weeks. RESULTS: No gender difference in inhibin A and activin A levels were observed. Inhibin B levels were significantly higher in males than in females (P < 0.05). Fetuses with the highest levels of inhibin A and B were found in the IUGR group that also showed activin A levels significantly higher than normal. No correlations were observed between inhibin A, inhibin B, activin A and both gonadotropins. CONCLUSION: Plasma inhibin A, inhibin B and activin A are detectable in both genders during intrauterine life. The different gender pattern of inhibin B suggests that inhibin B may contribute to the assessment of the hypothalamic-pituitary-gonadal set-point at least in males.

Effective salvage therapy with carboplatin/mitomycin C in metastatic breast cancer.

BACKGROUND: Alternative and effective drug regimens in patients with metastatic breast cancer progressing after adriamycin- and taxoid-containing regimens are urgently needed. PATIENTS AND METHODS: In a phase II trial, 43 heavily pretreated patients with metastatic breast cancer were treated with both carboplatin 200 mg/m(2) i.v. and mitomycin C 10 mg/m(2) i.v. on day 1 every 4 weeks. In case of granulocytopenia or thrombocytopenia below grade 3 according to NCI-CTC, the carboplatin dosage was escalated to 300, 400, and 450 mg/m(2) in the next treatment cycle. RESULTS: During the first 3 cycles the dose intensity of carboplatin could be increased from a mean of 50 to 74 mg/m(2)/week. Beyond this value the carboplatin dose intensity decreased because of hematotoxicity. Based on an intention-to-treat analysis, 9 of 43 patients responded to therapy (21%; 95% CI = 10.04-36.04) including 2 complete and 7 partial responses. 15 patients had no change, 13 progressed, and 6 patients were considered nonevaluable. The median time to progression was 3 (range 0-12) months. NCI-CTC grade 3 or 4 granulocytopenia was observed in 14 patients, grade 3 or 4 thrombocytopenia occurred in 32, grade 3 infections in 3, grade 3 hemorrhage in 1, and grade 3 cardiac dysrhythmias in 1 of the patients. CONCLUSIONS: In anthracycline/ taxoid-pretreated patients, salvage treatment with a combination of carboplatin and mitomycin C seems to be effective and associated with foreseeable toxicity. Based on our results with an intraindividual dose escalation of carboplatin, a dosage of 300 mg/m(2) in combination with mitomycin C 10 mg/m(2) every 4 weeks seems to represent a recommendable starting dose for future studies.

Prefrontal gray matter volume reduction in first episode schizophrenia.

Functional measures have consistently shown prefrontal abnormalities in schizophrenia. However, structural magnetic resonance imaging (MRI) findings of prefrontal volume reduction have been less consistent. In this study, we evaluated prefrontal gray matter volume in first episode (first hospitalized) patients diagnosed with schizophrenia, compared with first episode patients diagnosed with affective psychosis and normal comparison subjects, to determine the presence in and specificity of prefrontal abnormalities to schizophrenia. Prefrontal gray and white matter volumes were measured from first episode patients with schizophrenia (n = 17), and from gender and parental socio-economic status-matched subjects with affective (mainly manic) psychosis (n = 17) and normal comparison subjects (n = 17), age-matched within a narrow age range (18--29 years). Total (left and right) prefrontal gray matter volume was significantly reduced in first episode schizophrenia compared with first episode affective psychosis and comparison subjects. Follow-up analyses indicated significant left prefrontal gray matter volume reduction and trend level reduction on the right. Schizophrenia patients showed 9.2% reduction on the left and 7.7% reduction on the right compared with comparison subjects. White matter volumes did not differ among groups. These data suggest that prefrontal cortical gray matter volume reduction is selectively present at first hospitalization in schizophrenia but not affective psychosis.

Laser treatments with verteporfin therapy and its potential impact on retinal practices.

BACKGROUND: In the 1990s, the only available treatment for neovascular age-related macular degeneration (ARMD) was laser photocoagulation, but a minority of patients could be treated. Photodynamic therapy with verteporfin potentially allows many more patients to be treated. The authors' aim was to assess the impact of this increase on retinal practices. METHODS: The number of patients who received laser photocoagulation in 1998 was determined. Based on that number and a retrospective review of 1000 consecutive records of new patients with ARMD referred to the Associated Retinal Consultants practices during 1998, estimates were made of how many patients would have been eligible for verteporfin therapy. RESULTS: Of the 1000 patients, 171 had predominantly classic subfoveal choroidal neovascularization secondary to ARMD and would have been eligible for verteporfin therapy, compared with 99 treated with laser photocoagulation according to Macular Photocoagulation Study guidelines. If this patient population is representative of the general population, approximately 84,000 patients would be eligible for verteporfin therapy in the United States per year, compared with 42,000 for laser photocoagulation. This would lead to 286,000 verteporfin treatments per year if retreatments are required. CONCLUSIONS: This increase in treatments for neovascular ARMD will have a considerable impact on retinal practices. Although the resources that will need to be expended are high, the potential benefit of verteporfin therapy in reducing vision loss will outweigh the costs.

Impact of cytotoxic treatment on long-term fertility in patients with germ-cell cancer.

More than half of the patients with testicular germ-cell cancer show impaired spermatogenesis before undergoing cytotoxic treatment. The known pre-treatment infertility and the reversibility of the fertility problems observed in some after successful anti-cancer treatment have so far prevented an assessment of the true role of cytotoxic therapy in long-term fertility. The introduction of wait-and-see strategies (surveillance) for testicular cancer patients and recent prospective trials comparing patients with and without cytotoxic treatment have provided the means for estimating the extent to which treatment itself affects long-term fertility. Whether or not spermatogenesis is irreversibly impaired by chemotherapy is determined by the cumulative dose of cisplatin: at doses below 400 mg/m2, long-term effects on sperm production as well as on endocrine function are unlikely to occur. Higher doses should be expected to cause long-term losses of exocrine and endocrine gonadal function. In contrast, for adjuvant retroperitoneal radiotherapy in stage I seminoma patients, no data are available comparing long-term gonadal function with patients on surveillance. However, using modern radiation techniques, radiation doses to the para-aortic field (< 30 Gy) and testis shielding providing testis scatter radiation (< 30 cG), radiation-induced impairment of fertility is very unlikely.

Influence of helical CT parameters on spatial resolution in CT angiography performed with a subsecond scanner.

RATIONALE AND OBJECTIVES: In helical CT, the beam collimation, table feed (TF) per tube rotation, voltage, current, reconstruction increment, kernel, linear interpolation algorithm (LIA), and contrast are variable parameters. The purpose of this study was to determine which of these parameters are most important to minimize partial volume effects for improving spatial resolution in CT angiography. METHODS: Phantom vessel stenoses of different lengths (2, 8 mm) and diameters (0.5, 1, 2, 3, 4 mm) were scanned with helical CT using a constant tube rotation time of 0.75 sec and 42 selected combinations of the above-mentioned parameters. Orthogonal targeted maximum intensity projections of the stenoses were ordered according to the increase in blurring and noise in a consensus reading by two radiologists blinded to the parameters used. RESULTS: Three millimeters of collimation and TF in conjunction with a 180 degrees LIA and > 250 Hounsfield unit contrast density was considered the optimal parameter combination and enabled a continuous visualization of the stenoses down to 0.5 mm in diameter. A collimation of 1 or 2 mm and 5 mm was considered inferior to a collimation of 3 mm because of, respectively, noise and blurring. With 3 mm collimation, significant blurring occurred when a pitch larger than 1.5 was used. A 3 mm collimation with a pitch of 2 (6 mm TF) was found to be superior to a collimation of 5 mm in conjunction with a pitch of 1 (5 mm TF). With 5 mm collimation, the short stenoses could be visualized only when using a 180 degrees LIA and a TF per tube rotation smaller than 7 mm. Eight and 10 mm collimations failed to depict the short stenoses. CONCLUSIONS: Collimation had the most influence on image quality in CT angiography, followed by LIA, pitch, and contrast density. Decreasing the reconstruction increment to less than one third of the TF or increasing the voltage or current beyond standard values did not improve the delineation of the stenoses. For screening examinations, the authors recommend the use of 3 mm collimation, 180 degrees LIA, and a pitch of 2.

99mTc SESTAMIBI scintigraphic evaluation of skeletal muscle disease in patients with systemic sclerosis: diagnostic reliability and comparison with cardiac function and perfusion.

The diagnosis of skeletal muscle involvement in patients with systemic sclerosis (SSc) is usually based on clinical, laboratory, electromyographic, and bioptic evidence of muscle disorder, whereas SSc cardiac disease is well established by nuclear medicine techniques (radionuclide ventriculography and myocardial scintigraphy). Previous reports have retrospectively hypothesized a possible relationship between cardiac and muscle involvement in scleroderma patients. In order to improve overall diagnostic accuracy in the qualitative/quantitative assessment of skeletal muscle involvement in these patients and to compare these results with those obtained at the cardiac level, diethylenetriaminepentaacetic acid (DTPA)-99mTc radionuclide ventriculography and 99mTc SESTAMIBI myocardial and muscular scintigraphic examinations were performed in 10 SSc patients and in five healthy subjects. Muscular radioactivity, as assessed at thigh and calf levels by means of a segmental score, was significantly decreased in SSc patients in comparison with healthy subjects (global score value 15.6+/-2.2 vs 22.7+/-1.6, p<0.001), as well as right ventricular ejection fraction (RVEF, 34.3%+/-5.3 vs 53.6%+/-4.2, p<0.001) and myocardial segmental perfusion (global score value, 19.6+/-2 vs 25.9+/-1.1, p<0.01). The results show a high frequency of skeletal muscle involvement in patients with SSc. Moreover, scleroderma patients with muscle disorders, as evidenced by scintigraphy, show a comparable occurrence of cardiac involvement, even in the absence of clinical signs of cardiac dysfunction.

Presence of a p53 gene deletion in patients with multiple myeloma predicts for short survival after conventional-dose chemotherapy.

In multiple myeloma (MM), previous studies showed that mutations of the p53 gene are rare events in patients with newly diagnosed disease, but it is not known whether deletions of p53 are of any significance in MM. To address this question, we used interphase fluorescence in situ hybridization (FISH) with a DNA probe specific for the p53 locus at 17p13 and investigated bone marrow plasma cells from 72 patients with MM (59 patients = 81.9% before therapy). By FISH, deletions of p53, which were found to be predominantly monoallelic, were detected in 32.8% and 54.5% of patients with newly diagnosed and relapsed MM, respectively. Karyotypes from six of the patients with a p53 deletion by FISH showed a structural abnormality of 17p in only one of them. Additional FISH studies including a distal-17p probe (specific for the D17S34 locus) provided evidence for an interstitial deletion on 17p resulting in loss of p53 hybridization signals in myeloma cells. Among all 59 patients with newly diagnosed MM, presence of a p53 deletion was associated with stage III (P = .054), but not with other laboratory and clinical parameters. Patients with a p53 deletion had significantly shorter survival time compared with those without a deletion, both from the time of diagnosis (median 13.9 v 38.7 months; P < .0001) and from the time of initiation of induction treatment consisting of conventional dose chemotherapy (median 15.9 months v median not reached at 38 months; P < .0002). On stepwise multivariate regression analysis, presence of a p53 deletion was the most significant independent parameter predicting for shortened survival (P = .002). We conclude that a p53 gene deletion, which can be identified by interphase FISH in almost a third of patients with newly diagnosed MM, is a novel prognostic factor predicting for short survival of MM patients treated with conventional-dose chemotherapy.

Purification and characterization of a recombinant human cripto-1 protein.

Cripto-1 (CR-1) is a novel protein that contains a modified EGF-like motif and that does not directly bind to any of the known erb B type-1 receptor tyrosine kinase receptors. To more clearly define the biological effects of CR-1 and to more adequately compare the structure-function relationships of CR-1 with other members of the EGF family of growth factors, we have expressed a modified, full-length recombinant human CR-1 protein (rhCR-1) in E. coli and have devised a procedure for the solubilization, refolding and purification of a biologically active form of this protein. We have generated the mature form of hCR-1 from computer assisted predictions of potential signal peptide cleavage sites. Expression of the modified rhCR-1 protein in E. coli was limited to the inclusion bodies. The rhCR-1 protein was found to be expressed at high levels in bacterial cells when fused to a histidine-tag sequence. Refolding of rhCR-1 was found to be difficult because of the large number of cysteine residues in the protein which results in protein aggregation. By chemically modifying the cysteine residues in the rhCR-1 protein with 3-trimethylammoniopropyl methanethiosulfonate, additional positive charges have been introduced into the protein by this disulfiding reagent. This modification facilitates solubilization of the protein when rhCR-1 is denatured. The solubilized, denatured protein was then purified by CM cation exchange and C4 reverse phase HPLC chromatography and refolded in a redox buffer. The refolded, modified rhCR-1 protein was found to be biologically active by its ability to inhibit beta-casein expression, to stimulate the tyrosine phosphorylation of Shc and the activation of MAPK and by its capacity to facilitate branching growth of mouse mammary epithelial cells in type I collagen gels.

Chemical synthesis, structural modeling, and biological activity of the epidermal growth factor-like domain of human cripto.

Cripto, also known as human teratocarcinoma-derived growth factor 1 (TDGF-1), contains a 40 amino acid region with some similarity to the epidermal growth factor (EGF) domain. However, sequence homology is largely restricted to the classical cysteine/glycine motif with only limited similarities in other regions. Significant differences to human EGF include the absence of all seven residues between the two N-terminal half-cystines and a five-residue shorter loop between the third and fourth half-cystines. We examine the hypothesis that, in spite of these differences, cripto can adopt the characteristic EGF-like 1-3, 2-4, 5-6 disulfide bond pattern. A comparative structural model of the growth factor cripto was constructed on the basis of its similarity to EGF, transforming growth factor alpha (TGF-alpha), and the EGF-like domain of human clotting factor IX. The predicted disulfide bridges and disulfide-bridged loops were analyzed and appear viable in the modeled structure. Moreover, to ascertain the importance of disulfide arrangement for cripto bioactivity, two 47-residue peptides were synthesized and then refolded using either a simple oxidative or a controlled sequential refolding protocol. The cripto peptides were tested for their ability to stimulate MAP-kinase activity, for inhibition of beta-casein induction, and for Shc phosphorylation in MDA-MB 453 human mammary carcinoma cells and HC-11 mouse mammary epithelial cells. Data suggest that cripto does adopt the 1-3, 2-4, 5-6 disulfide pattern and thus forms the classical EGF-like fold in spite of the significant deletions within the folding domain. The predicted structure of cripto shows some of the characteristics of both the ErbB1- and ErbB3/ErbB4-binding growth factors.

Encapsulated sensory receptors within intraorbital skeletal muscles of a camel.

BACKGROUND: The occurrence of encapsulated sensory receptors in extrinsic ocular muscles differs among and within orders of mammals. Beyond indications that neuromuscular and neurotendinous spindles are present in extraocular muscles of the family Camilidae, little is known of their distributional characteristics. In fact there appear to be no distribution maps for any animal that show both major types of encapsulated muscle receptor in a full set of intraorbital skeletal muscles. METHOD: Serial histological sections of all skeletal muscles from one orbit of an adult, one-humped camel (Camelus dromedarius) were examined for encapsulated receptors. RESULTS: Encapsulated receptors were apparent in all the intraorbital skeletal muscles. Muscle spindles outnumbered tendon organs in the fleshy part of each muscle. For all muscles, spindles were most abundant in the half of the muscle near the origin; levator palpebrae superioris had a more even distribution of spindles along its length than did extraocular muscles. These longitudinal patterns of distribution for muscle spindles related in a general way to the nerve entry zone. Tendon organs occurred anywhere along a muscle's length, but they tended to be more frequent on either side of the major concentration of muscle spindles. Both types of encapsulated receptors were generally located nearer the perimeter than the center of cross sections through muscles. CONCLUSIONS: Encapsulated receptors of classic appearance are plentiful and have distinctive configurations within intraorbital skeletal muscles of the adult dromedary. When analyzed in conjunction with other studies, the present data give rise to testable explanations for the variability among genera in the number of encapsulated receptors in extraocular muscles.

Rat gestation during space flight: outcomes for dams and their offspring born after return to Earth.

Sprague-Dawley rats were studied to learn whether gestation in the near-zero gravity, high radiation environment of space impacts selected mammalian postnatal events. Ten rats spent days nine to twenty of pregnancy aboard the space shuttle orbiter Atlantis (STS-66). Their movement was studied shortly after return to Earth; subsequently, several of their offspring were cross-fostered and examined through postnatal day 81 (P81) for whole body growth and somatic motor development. Values for the flight animals were compared to ground-based control groups. Relative to controls, the pregnant flight rats showed a marked paucity of locomotion during the first few hours after returning to Earth. There was greater likelihood of perinatal morbidity for the offspring of flight dams when compared to the control groups. Whole body weight of surviving offspring, averaged for each group separately, showed typical sigmoidal growth curves when plotted against postnatal age. The flight group for our study had a larger ratio of female to male pups, and that was sufficient to account for the lower average daily weight gained by the flight animals when compared to the control groups. Walking was universally achieved by P13 and preceded eye opening, which was complete in all pups by P17. Thus, both of these developmental horizons were attained on schedule in the flight as well as the control rats. Characteristic changes were observed in hind limb step length and gait width as the pups grew. These patterns occurred at the same time in each group of rats. Therefore, prenatal space flight from days nine to twenty of gestation did not interfere with the establishment of normal patterns for hind paw placement during walking.

Hormone levels in centenarians.

The serum profiles of total triiodothyronine (T(3)), free thyroxin (fT(4)), thyroid stimulating hormone (TSH), cortisol, prolactin (HPRL), parathormone (PTH), osteocalcin and growth hormone (GH) were measured in a group of 12 centenarians and compared to the values of a control group of twenty-nine subjects, aged 67-98 years. The study was aimed at revealing whether there are appreciable differences or age-related modifications in the hormone status of healthy control elderly and the centenarian population. In this series, the modifications in hormone levels were unremarkable, and the serum levels of the studied hormones in centenarians often fell within a range considered to be normal for the younger age classes.

Preoperative identification of perforating vessels to the skin by color duplex imaging.

Recent improvements in high-frequency linear array transducers with color duplex imaging permit the precise identification and estimation of the caliber of minute perforating vessels to the skin as small as 0.5 mm. An obvious corollary role would be the accurate preoperative delineation of the vascular anatomy of a skin flap, which could be essential to ensure its viability. This technology was then applied to map the blood supply to skin flaps in eight patients, which was subsequently verified at the time of their actual surgical dissection. Because anomalies of the skin circulation are not uncommon, this extended capability for color duplex imaging can facilitate a more optimal design of skin flaps to better ensure their chance for survival by the inclusion of appropriate nutritive blood vessels.

Correlative light and electron microscopic study of boutons on neuronal somas isolated from fixed mammalian brain.

Procedures are described for isolating neuronal somas by ultrasonic disruption of fixed rat brain and for fashioning a device that facilitates studying the same single soma by light microscopy and scanning and transmission electron microscopy. The device enables one to carry and repeatedly locate individual cells as well as hold solutions used to bathe the cells. Sequential electron microscopic examination of individual somas was used to confirm the presence of axosomatic boutons at the surface of isolated neurons.

Location and completeness of reinnervation by two types of neurons at a single target: the feline muscle spindle.

Muscle spindles from the tenuissimus muscle of the cat were examined microscopically to assess the precision and completeness of reinnervation of intrafusal muscle fibers by efferent and afferent neurons. Positions of motor and sensory nerve terminals were charted relative to the cross-sectional area enclosed by the outer capsule of the spindle. Profiles of nerve endings were measured for normally innervated and reinnervated spindles. The tenuissimus was deprived of innervation by freezing its nerve, sometimes in conjunction with either spinal ganglion removal or ventral rhizotomy. Sensory and motor terminals occupied separate locales along the length of normal muscle spindles. Nerve terminals of efferent and afferent neurons were located in appropriate positions along the length of spindles when axons of both types of neurons regrew together and when either category of axon regenerated alone. Precise reinnervation of muscle spindles occurred in spite of a diminished diameter of intrafusal fibers. Repopulation of the spindle with motor endings was less complete than that by sensory endings, based on the proportion and size of the regenerated terminals. We conclude that under optimal conditions for axonal regrowth, efferent and afferent neurons reinnervate their respective regions along intrafusal muscle fibers but motor lags sensory reinnervation within the spindle. The mechanism by which positional specificity happens during reinnervation of intrafusal fibers requires neither an interaction between terminals of the two types of neurons nor target cells of normal bulk.

Porcelain color plates for immunohistochemical incubation of free-floating tissue sections.

Porcelain color plates are a convenient alternative to multiwell plastic plates for immunohistochemical incubations. The advantage of the plates are that they allow relatively large tissue sections to float freely in small volumes of liquid and allow easy access to the sections.