Computer identification of neoplastic urothelial nuclei from the bladder.

OBJECTIVE: To introduce computer-based analysis of Feulgen-stained urinary bladder cell nuclei from voided urine to identify neoplastic urothelial nuclei. STUDY DESIGN: Nuclei from 23 healthy people and 33 patients with urinary bladder cancer were analyzed. The nuclei from 9 cancer patients with grade G1 (stage Ta), 17 with grade G2 (stages Ta, T1, T1a and T2) and 7 with grade G3 (stages Cis, Ta + Tis, T1 and T3b) were analyzed. Image analysis was carried out by means of a digital image processing system designed by the authors. Features describing nuclei were selected as the first step of the procedure. Then a multistage classifier was constructed to identify positive and negative cases. RESULTS: The results of this pilot study of a group of 56 patients yielded a 71% correct classification rate in the control group, while a 66% rate was obtained among the cancer patients. The sensitivity of the method was 100% and the specificity was 77%. CONCLUSION: This approach to the identification of neoplastic urothelial nuclei may be sufficiently well developed to be used successfully both in screening high-risk populations and in clinical practice.     

The relative roles of aggressive wound care versus revascularization in salvage of the threatened lower extremity in the renal failure diabetic patient

Current literature indicates poor survival and limb salvage rates in renal failure diabetic patients who present with ulcerated or gangrenous lower extremities. Even in those limbs that were successfully revascularized, the amputation rate was as high as 37 percent. This has led some to advocate immediate amputation when treating the threatened limb of a renal failure diabetic patient. The authors reviewed all renal failure diabetic patients in their wound registry to determine whether such pessimism was warranted. The authors then analyzed the relative roles of revascularization and aggressive wound care on long-term limb salvage. Forty-five consecutive renal failure diabetic patients with 71 wounds in 54 limbs were identified. Twenty-seven patients had chronic renal insufficiency, 15 patients had end-stage renal disease, and three patients received kidney transplants. The revascularization procedures (46 percent of all limbs) included angioplasty, femoral-popliteal, femoral-distal, and popliteal-distal bypasses. Forty-three amputations in combination with 67 soft-tissue repairs (delayed primary wound closure, skin grafts, local flaps, pedicled flaps, and free flaps) were necessary to close the defects. After a mean follow-up of over 3 years, the data indicate that 79 percent of wounds healed, 89 percent of all limbs were salvaged, and 49 percent of patients survived. Revascularization improved the threatened limb's salvage rate from negligible to a level similar to that of the adequately vascularized limb. Fifteen out of 71 wounds did not heal because of the patient's early postoperative death, ischemia not amenable to revascularization, or noncompliance. Six below-knee amputations were performed (one despite a patent bypass and five in adequately vascularized patients). The average time for wounds to heal in the revascularized patients was 79 days versus 71 days in adequately vascularized patients. There was an overall 43 percent complication rate. Of the patients who were alive after the 3-year follow-up, 73 percent were independently ambulating, whereas 27 percent were bound to wheelchair or bed. Eighty-two percent of patients were very satisfied with the salvage attempt, 18 percent were moderately satisfied, and all patients said they would go through the process again. The authors believe that salvaging the threatened extremity in the renal failure diabetic patient is justified whether or not the limb requires revascularization. Revascularization improved the limb salvage rate, patient survival, and days for wounds to heal to a level comparable to that of the adequately vascularized limb. The key to subsequently achieving high salvage rates is the quality of perioperative wound care (e.g., serial debridements, antibiotics, dressings) and the timing and selection of appropriate soft-tissue coverage.     

High-dose Insulin Therapy: is it Time for U-500 Insulin?

ObjectiveTo provide an overview of U-500 regular insulin action, review published clinical studies with U- 500 regular insulin, and offer guidance to practicing endocrinologists for identifying patients for whom U-500 regular insulin may be appropriate.MethodsThis review has been produced through a synthesis of relevant published literature compiled via a literature search (MEDLINE search of the English-language literature published between January 1969, and July 2008, related to U-500, insulin resistance, concentrated insulin, high-dose insulin, insulin pharmacokinetics, and diabetes management) and the authors’ collective clinical experience.ResultsThe obesity epidemic is contributing to an increase in the prevalence of type 2 diabetes, as well as to increasing insulin requirements in insulin-treated patients. Many of these patients exhibit severe insulin resistance, manifested by daily insulin requirements of 200 units or greater or more than 2 units/kg. Delivering an appropriate insulin volume to these patients can be difficult and inconvenient and may be best accomplished with U-500 regular insulin by multiple daily injections or with continuous subcutaneous insulin infusion, rather than with standard U-100 insulin. Implementation of U-500 regular insulin in patients previously on other insulin formulations is described with a treatment algorithm covering dosage requirements ranging from 150 to more than 600 units per day on the basis of the authors’ experience.ConclusionRegimen conversion of appropriately selected patients from high-dose, U-100 insulin to U-500 regular insulin therapy on the basis of the recommendations presented in this article may potentially result in improved glycemic control and lower cost. (Endocr Pract. 2009;15:71-79)     

Long-term results of MISTI gold breast implants: a retrospective study

MISTI Gold breast implants (Bioplasty, St. Paul, Minn.) filled with polyvinylpyrrolidone-hydrogel were developed as a promising alternative to silicone-filled implants. Some studies have reported on the positive effects of the implant, such as improved radiolucency and biocompatibility of the gel; however, there are also reports that such implants increased in volume and were subject to capsular contracture in the human body, resulting in demands for their removal. The purpose of this retrospective study was to analyze the long-term results of a series of patients with MISTI Gold breast implants. Between 1991 and 1993, the authors inserted 83 MISTI Gold implants in 61 patients with an average age of 46 years (range, 16 to 69). The authors were able to follow up 48 patients with 71 MISTI Gold implants. The average follow-up was 68 months (range, 10 to 108 months). The retrospective study found that 59 percent of all MISTI Gold implants were removed after an average period of 4.14 years. The main reason for implant removal was an increase in volume of 38 percent, followed by capsular contracture in 14 percent of all 71 MISTI Gold implants. The average increase in volume of all removed MISTI Gold implants was 43 percent. Capsular contracture was graded as Baker I and II in 63 percent and as Baker III and IV in 37 percent. In conclusion, the authors believe that MISTI Gold implants do not fulfill the criteria of safe breast implants, and they agree with the December of 2000 opinion of the Medical Devices Agency of the Department of Health in London that the hydrogel-filled breast implants should not be used until more information about the filler material and its metabolic fate is available.     

The role of laparoscopy in the surgical treatment of colorectal cancer. Initial results

The authors have carried out laparoscopically assisted abdomino-perineal rectal resections on a selected group of 8 patients during the past two years. The laparoscopic technique was not accompanied by any complications, while the patients enjoyed the benefits of the procedure. The bowel function of the patients were restored on the 2nd to 3rd day, the mean length of the hospital stay was 8.3 days. On the basis of their own favourable initial experience and recent literature data, the authors discuss the benefits, disadvantages and pitfalls of the laparoscopically assisted technique for surgical treatment of colorectal cancer. The problematics of oncological radicality is analysed.     

UNC-71, a disintegrin and metalloprotease (ADAM) protein,regulates motor axon guidance and sex myoblast migration in C. elegans

The migration of cells and growth cones is a process that is guided by extracellular cues and requires the controlled remodeling of the extracellular matrix along the migratory path. The ADAM proteins are important regulators of cellular adhesion and recognition because they can combine regulated proteolysis with modulation of cell adhesion. We report that the C. elegans gene unc-71 encodes a unique ADAM with an inactive metalloprotease domain. Loss-of-function mutations in unc-71 cause distinct defects in motor axon guidance and sex myoblast migration. Many unc-71 mutations affect the disintegrin and the cysteine-rich domains, supporting a major function of unc-71 in cell adhesion. UNC-71 appears to be expressed in a selected set of cells. Genetic mosaic analysis and tissue-specific expression studies indicate that unc-71 acts in a cell non-autonomous manner for both motor axon guidance and sex myoblast migration. Finally, double mutant analysis of unc-71 with other axon guidance signaling molecules suggests that UNC-71 probably functions in a combinatorial manner with integrins and UNC-6/netrin to provide distinct axon guidance cues at specific choice points for motoneurons.     

Serine-71 phosphorylation of rac1 modulates downstream signaling

The Rho GTPases Rac1 and Cdc42 regulate a variety of cellular functions by signaling to different signal pathways. It is believed that the presence of a specific effector at the location of GTPase activation determines the route of downstream signaling. We previously reported about EGF-induced Ser-71 phosphorylation of Rac1/Cdc42. By using the phosphomimetic S71E-mutants of Rac1 and Cdc42 we investigated the impact of Ser-71 phosphorylation on binding to selected effector proteins. Binding of the constitutively active (Q61L) variants of Rac1 and Cdc42 to their specific interaction partners Sra-1 and N-WASP, respectively, as well as to their common effector protein PAK was abrogated when Ser-71 was exchanged to glutamate as phosphomimetic substitution. Interaction with their common effector proteins IQGAP1/2/3 or MRCK alpha was, however, hardly affected. This ambivalent behaviour was obvious in functional assays. In contrast to Rac1 Q61L, phosphomimetic Rac1 Q61L/S71E was not able to induce increased membrane ruffling. Instead, Rac1 Q61L/S71E allowed filopodia formation, which is in accordance with abrogation of the dominant Sra-1/Wave signalling pathway. In addition, in contrast to Rac1 transfected cells Rac1 S71E failed to activate PAK1/2. On the other hand, Rac1 Q61L/S71E was as effective in activation of NF-kappaB as Rac1 Q61L, illustrating positive signal transduction of phosphorylated Rac1. Together, these data suggest that phosphorylation of Rac1 and Cdc42 at serine-71 represents a reversible mechanism to shift specificity of GTPase/effector coupling, and to preferentially address selected downstream pathways.     

Relationship between insulin and somatotropin in obesity.

The authors have estimated a correlation between the total insulin areas after glucose loading and total somatotropin areas during insulin-induced hypoglycaemia in 30 patients with obesity, as well as in a selected group of 16 patients with simple (essential) obesity. A significant negative correlation was found in both investigated groups. A new hypothesis assuming hyposecretion of somatotropin in obese subjects as a result of hyperinsulinaemia and subsequent increased somatomedin generation is suggested.     

Prevalence of TT virus in patients with hepatitis B,C and hepatitis of unknown etiology

Discovery of TT virus in 1997 gave raise to intensive subsequent studies to learn about its structure, features and, what is the most important, about its role in pathogenesis of liver disease. The aim of the work was to analyze prevalence of TTV DNA in patients with diagnosed hepatitis B, C, that of unknown etiology and in healthy blood donors as well. Additionally the divergence of TTV sequence was estimated in selected cases. TTV DNA was detected by PCR technique using specific oligonucleotide primers for coding regions. TT virus has been detected in 25.6% (32/125) HBsAg positive patients and in 23.9% (51/213) HCV infected patients. In healthy blood donors the frequency of TTV was 24.3% (34/140) similarly to that found in HCV and HBV infected patients. The frequency of TTV DNA among patients with hepatitis of unknown etiology was 9.1%. This result was statistically significant lower than in the other groups. When detected sequences have been compared to these from NCBI base the homology result was 71% to 95%, and among different patients and groups of patients identity was 46% to 73%. On the basis of the obtained results it can be concluded that it is very unlikely that TTV coinfection plays any significant role in HCV or HBV infection. The hypothetical role of TTV infection in the etiopathogenesis of cryptogenic chronic hepatitis has not been confirmed. The results obtained in the small group of patients with hepatitis of unknown etiology are not conclusive and should be taken with some precaution. The final conclusion is the TTV coinfection does not contribute to the liver pathology. The divergence of TTV sequences may explain the various frequency of TTV viremia reported by other authors.     

Immunotherapy with CD25/CD71-allodepleted T cells to improve T-cell reconstitution after matched unrelated donor hematopoietic stem cell transplant: a randomized trial

Background aimsDelayed immune reconstitution is a major challenge after matched unrelated donor (MUD) stem cell transplant (SCT). In this randomized phase 2 multi-center trial, Adoptive Immunotherapy with CD25/71 allodepleted donor T cells to improve immunity after unrelated donor stem cell transplant (NCT01827579), the authors tested whether allodepleted donor T cells (ADTs) can safely be used to improve immune reconstitution after alemtuzumab-based MUD SCT for hematological malignancies.MethodsPatients received standard of care or up to three escalating doses of ADTs generated through CD25+/CD71+ immunomagnetic depletion. The primary endpoint of the study was circulating CD3+ T-cell count at 4 months post-SCT. Twenty-one patients were treated, 13 in the ADT arm and eight in the control arm.ResultsThe authors observed a trend toward improved CD3+ T-cell count at 4 months in the ADT arm versus the control arm (230/µL versus 145/µL, P = 0.18), and three ADT patients achieved normal CD3+ T-cell count at 4 months (>700/µL). The rates of significant graft-versus-host disease (GVHD) were comparable in both cohorts, with grade ≥2 acute GVHD in seven of 13 and four of eight patients and chronic GVHD in three of 13 and three of eight patients in the ADT and control arms, respectively.ConclusionsThese data suggest that adoptive transfer of ADTs is safe, but that in the MUD setting the benefit in terms of T-cell reconstitution is limited. This approach may be of more use in the context of more rigorous T-cell depletion.     

The value of the x-ray study method in the diagnosis of celiac-sprue]

The authors describe some features of x-ray symptoms of Gee-Herter disease with relation to severity and a period of disease. Altogether 106 adult patients with this disease were followed up, of them 78 patients with diagnosis of Gee-Herter disease, confirmed by histology of intestinal biopsy specimens, were selected for analysis. Three groups of patients with different x-ray symptoms were singled out. Some distinctive features of differential diagnosis and complications of Gee-Herter disease in adults were noted.     

A novel promoter polymorphism (-71C>T) in KRTHB6 gene in Indian population

We have screened the basal promoter region, of KRTHB6 gene involving CAAT and TATA boxes in randomly selected 125 individuals of Indian origin by PCR-SSCP and DNA sequencing. We observed a novel promoter polymorphism (-71C>T) which could be differentiated by using LweI restriction enzyme. The frequency of -71 C allele, allele A (Accession no AY203963), was observed to be higher ( 0.712) in comparison to -71 T allele, allele B (0.288) (Accession no. AY037552).     

Cytometric evaluation of transferrin receptor 1 (CD71) in childhood acute lymphoblastic leukemia

Transferrin receptor 1 (CD71) is a transmembrane glycoprotein responsible for cellular iron uptake. Higher expression of CD71 has been identified as a negative prognostic marker for numerous solid tumor types and for some lymphomas. The aim of this study was to evaluate CD71 expression on acute lymphoblastic leukemia (ALL) cells and to follow its possible clinical correlations. Sixty one patients, aged 1-17 years and diagnosed with ALL, were enrolled in the study. CD71 expression was analyzed on the bone marrow blastic cells by flow cytometry. CD71 expression on the leukemic blasts was diversified; in most patients, all blastic cells showed expression of CD71, but levels of expression varied. CD71 expression was statistically higher on T-lineage leukemias. Within the B lineage ALL, a significant difference in CD71 expression existed between precursor B ALL and mature B-ALL, which showed higher CD71 expression. CD71 expression positively correlated with Hgb concentration at diagnosis. Initial risk group assessment and therapy response were not correlated with CD71 expression, although disease free and overall survival times tended to be shorter in patients with B-lineage leukemias with initial high CD71 expression.     

The deep inferior epigastric perforator flap for breast reconstruction in overweight and obese patients

The authors retrospectively reviewed the computerized records of 71 women undergoing 80 deep inferior epigastric perforator (DIEP) flap reconstructions after mastectomy over a 1-year period. There were 33 normal, 26 overweight, and 12 obese patients. No statistically significant difference in flap complications was found between groups. Overall fat necrosis rates were 11.4 percent for the normal-weight patients, 6.7 percent for the overweight patients, and 6.7 percent for the obese patients. Postoperative hospital time was similar for all groups. The occurrence of abdominal wall fascial laxity was uncommon and similar for all groups. Large (>900 g) reconstructions were completed without prohibitive complications in the reconstruction flap. The DIEP flap represents a significant advance in autologous breast tissue reconstruction. Although concerns regarding fat necrosis rates in DIEP flaps have been voiced, the authors did not see an increasing rate of fat necrosis in their overweight and obese patients, and their overall rate of fat necrosis is comparable to rates reported for free transverse rectus abdominis myocutaneous (TRAM) flaps. Also, increasing body mass index did not seem to affect the rate of delayed complications of the abdominal wall, such as abdominal wall hernia or bulging. Although it was not statistically significant, the authors did observe a trend toward increased wound-healing complications with increasing body mass index. Their data also support the claim that the complete sparing of the rectus abdominis muscles afforded by the DIEP flap avoids abdominal wall fascial bulging or defects often seen in obese TRAM reconstruction patients. Because flap and wound complication rates are similar or superior to those of other autologous tissue reconstruction techniques and the occurrence of abdominal wall defects is all but eliminated, the DIEP flap likely represents the preferred autologous breast reconstruction technique for overweight and obese patients.     

Depiction of facial nerve paresis in the gallery of portraits carved in stone by George Matthew the Dalmatian on the Sibenik Cathedral dating from the 15th century

The introductory segment of this paper briefly describes George Matthew the Dalmatian, the architect who, between 1441 and 1473, oversaw the construction of the Cathedral of St. James in Sibenik, a city on the Croatian side of the Adriatic coast. Of the most impressive details included in this monumental construction and sculptural flamboyant gothic production infused with distinctive Dalmatian spirit is a frieze of 71 stone and three lion portraits encircling the outer apse wall. From the intriguing amalgamation of portraits of anonymous people this master came across in his surrounding, the fiftieth head in the row has been selected for this occasion. On the face of a younger man the authors have recognized and described pathognomonic right-sided facial nerve paresis. The question posed here is whether this is coincidental or it represents the master's courage, given that instead of famous people in the cathedral he situated not only ordinary people but also those "labelled" and traditionally marginalized, thus, in the most beautiful manner, foreshadowing the forthcoming spirit of Humanism and Renaissance in Croatian and European art.     

Neuronal differentiation modulates the dystrophin Dp71d binding to the nuclear matrix

The function of dystrophin Dp71 in neuronal cells remains unknown. To approach this issue, we have selected the PC12 neuronal cell line. These cells express both a Dp71f cytoplasmic variant and a Dp71d nuclear isoform. In this study, we demonstrated by electron and confocal microscopy analyses of in situ nuclear matrices and Western blotting evaluation of cell extracts that Dp71d associates with the nuclear matrix. Interestingly, this binding is modulated during NGF-induced neuronal differentiation of PC12 cells with a twofold increment in the differentiated cells, compared to control cells. Also, distribution of Dp71d along the periphery of the nuclear matrix observed in the undifferentiated cells is replaced by intense fluorescent foci localized in the center of the nucleoskeletal structure. In summary, we revealed that Dp71d is a dynamic component of nuclear matrix that might participate in the nuclear modeling occurring during neuronal differentiation.     

Outbreak of central nervous system disease associated with hand,foot, and mouth disease in Japan during the summer of 2000: detection and molecular epidemiology of enterovirus 71

Few outbreaks of the serious enterovirus 71 (EV71) infections, which affect the central nervous system (CNS), had been reported in Japan before 2000. During June through August 2000, a patient died of pulmonary edema caused by brainstem encephalitis accompanied by EV71-induced hand, foot, and mouth disease (HFMD), and many patients complicated by serious CNS disease, including paralysis, were hospitalized in a restricted area in Hyogo Prefecture, Japan (K-area). During the same period, endemics of HFMD were reported in other areas in Hyogo Prefecture, where EV71 was isolated from HFMD patients, but few patients developed aseptic meningitis. The isolations of EV71 from K-area patients were difficult with the use of Vero cells, so the strains were isolated by use of GL37 cells; Vero cells, however, could isolate EV71 strains from other areas in Hyogo Prefecture. We sequenced VP4 coding regions of these EV71 isolates and found that the isolates from K-area had the same sequence, which, except for one isolate, was different from the sequences of EV71 strains isolated from other areas of Hyogo Prefecture. Although these results were not enough to state that EV71 from K-area was a virulent strain, it seemed reasonable to conclude that serious CNS diseases in K-area were caused by EV71 because it was the only infectious agent detected in the inpatients of K-area.     

高龄隐匿性冠心病患者围术期心血管功能异常研究

目的：探讨隐匿性冠心病（或无症状心肌缺血SMI）患者围术期的心血管功能异常及与年龄的相关性,探讨围术期心律失常的临床治疗和转归。方法：180例择期手术的无症状心肌缺血患者,年龄≥51岁者130例,按年龄将其分为51～60岁组、61～70岁组和71～80岁组,其余50例年龄≤50岁者为对照组。动态心电图连续记录患术前24h、术后24h、术后48h心电图信息,专业医师分析统计s11段下移及弓背样抬高的幅度、时间,各型心律失常、各时间段心律失常发生率等,同时记录临床治疗、效果及转归。结果：随年龄增加,ST段改变幅度及持续时间增大（P〈0．05,P〈0．01）;71～80岁组ST段弓背样抬高发生率大于对照组（P〈0．05）;61～70岁组ST段下移时间、71～80岁组ST段下移时间及弓背样抬高幅度大于51～60岁组（P〈0．05）。61～70岁组的加速性室性自主心率（A巩）发生率和71。80岁组的窦性的心动过缓（SB）、室性早搏（VPB）、室性心动过速（vT）发生率大于对照组（P〈0．05,P〈0．01）;61～70岁组的房颤（AF）发生率和71～80岁组的VP、VT及AF发生率大于51-60岁组（P〈0．05,P〈0．01）。各组术后24h心律失常发生率大于术后48h及术前24h（P〈0．01）;随年龄增加,排除诱因后可逆转的心律失常明显减少,需药物逆转和电学逆转者明显增加（P〈0．05）。结论：高龄SMI患者围术期心肌缺血及心律失常高发,且随着年龄的增加而增加,术后24h是心功能异常高发时段。     

Simple electrostimulator for clinical gustometry

The authors illustrate the technical characteristics of a low cost, pocket electrogustometer, which works on batteries and offers complete safety both for the patient and for the examiner; this model is able to carry out, both in normal and selected patients, the same functions as can be carried out with more sophisticated and costly equipment, currently available.