Tissue engineering of heart valves -- current aspects

Tissue engineering of heart valves is an evolving research field. Driven by the shortcomings of the heart valve substitutes currently available, such as need for anticoagulation, susceptibility to infections, inability to grow and autorepair, the multidisciplinary approach for designing and growing viable heart valves identical to the native heart valves has begun. The following will give an update of the recent developments, current limitations and potential future applications of tissue-engineered heart valves.     

Will transplantation of peripheral blood stem haematopoietic cells definitively replace bone marrow transplantation?

Findings assembled for a long time, practically from the end of the Second World War along with modern technology of genetic engineering which brought mass production of growth factors led at the beginning of the nineties of the 20th century to a rapid rise of transplantations of peripheral stem cells. Without exaggeration it may be said that the last decade of the 20th century is the decade of transplantations of peripheral stem cells. Peripheral stem cells comprise a wide range of haematopoietic cells incl. stem cells which are after a stimulus (antitumour chemotherapy or growth factors) released from bone marrow in high concentrations into the peripheral blood stream from where they can be obtained very simply by modern blood cell separators. They are suitable for autologous as well as allogenic transplantations. In autologous applications they have almost replaced bone marrow. Restoration of haematopoiesis is after their use more rapid as the transplant is richer. As regards allogenic application caution is still apparent, although even their ratio is very significant. However a higher rate of reactions of the graft to the host is feared. It seems however that this fear is not justified and that the richer transplant of peripheral stem cells can ensure a higher anti-tumourous effect of the transplantation. Peripheral stem cells are also used successfully in transplantations after so-called non-myeloablative regimes. It is beyond doubt that the use of peripheral stem cells will increase further. We may expect application of other growth factors with a higher mobilizing capacity. Peripheral stem cells will be subjected to further modifications in vitro. It will be also possible to increase their amount. A rich transplant makes it also possible to use it in transplantations from haploidentic donors. No doubt stem cell suspensions will become the objective of gene therapy.     

Lymphocytosis with large granular lymphocytes: case report

Lymphoproliferative disorders of large granular lymphocytes (LGL) can arise from either CD3+ T cells or CD3- natural killer cells. Polyclonal proliferation of LG lymphocytes is called LGL lymphocytosis, monoclonal proliferation of LG lymphocytes is LGL leukaemia. Prominent clinical manifestations of LGL lymphocytosis and leukaemia are bacterial infections, splenomegaly, and may be connected with rheumatic or autoimmune disorders. Hematologic findings reveal particularly lymphocytosis, and severe neutropenia. The beta chain gene of T cell receptor rearrangement analysis is necessary for distinguishing of T LGL lymphocytosis from T LGL leukaemia. The authors report a case of young woman with T cells LGL lymphroproliferative disorder, bacterial infection, reactive lymphadenopathy, and spontaneous regression of the lymphocytosis within 6 months.     

Dose-dependent effect of etoposide in combination with busulfan plus cyclophosphamide as conditioning for stem cell transplantation in patients with acute myeloid leukemia

To evaluate the efficacy and toxicity of two different etoposide (VP-16) dosages (30 or 45 mg/kg) in combination with busulfan/cyclophosphamide as conditioning therapy followed by stem cell transplantation in acute myeloid leukemia (AML), 90 patients with AML received either 30 mg/kg (n = 60) or 45 mg/kg (n = 30) etoposide in combination with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). The stem cell source was allogeneic related bone marrow (BM) (n = 53), allogeneic unrelated BM (n = 5), allogeneic unrelated peripheral blood (PBSC) (n = 2), syngeneic BM (n = 2), autologous BM purged (n = 9) or unpurged (n = 9), autologous PBSC (n = 10). Fifty-six patients (62%) were in first CR, 26 (29%) were > first CR, and eight (9%) were transplanted in relapse. Principal toxicities in both groups were mucositis and hepatotoxicity. Forty-five mg/kg etoposide resulted in greater hepatic toxicity (P = 0.03), and a higher incidence of VOD (23 vs 12%, P = 0.04) and acute GVHD grade III/IV (13 vs 5%, NS). The treatment-related mortality was 17% in the 30 mg/kg group and 33% in the 45 mg/kg group, mainly due to infections, intestinal pneumonia and GVHD. Hematological recovery of leukocytes 1/nl was comparable in both groups (17 vs 16 days). After a median follow-up of 16 months 19% in the 30 mg/kg group and 23% in the 45 mg/kg group relapsed. In patients who had undergone allogeneic related bone marrow transplantation in first CR no relapses occurred after a median follow-up of 3 years. For all patients the 3-year estimated disease-free survival was 62% in the 30 mg/kg group and 40% in the 45 mg/kg group (P = 0.03). For patients in first CR who underwent allogeneic related stem cell transplantation the 3 year disease-free survivals were 80% and 66%, respectively (P = 0.4). We conclude that etoposide 30 mg/kg or 45 mg/kg in combination with busulfan/cyclophosphamide is a highly active regimen for bone marrow transplantation of patients with AML with a low relapse rate. However, conditioning with 30 mg/kg rather than 45 mg/kg etoposide resulted in less toxicity and a better overall survival due to a lower transplant-related mortality. Bone Marrow Transplantation (2000) 26, 711-716.     

The impact of irritable bowel syndrome on health-related quality of life

BACKGROUND & AIMS: Few data are available to evaluate health-related quality of life (HRQOL) of people with irritable bowel syndrome (IBS). We evaluated and compared the impact of IBS on HRQOL using previously reported HRQOL data for the U.S. general population and for people with selected chronic diseases. METHODS: Using the SF-36 Health Survey, we compared the HRQOL of IBS patients (n = 877) with previously reported SF-36 data for the general U.S. population and for patients with gastroesophageal reflux disease (GERD), diabetes mellitus, depression, and dialysis-dependent end-stage renal disease (ESRD). RESULTS: On all 8 SF-36 scales, IBS patients had significantly worse HRQOL than the U.S. general population (P < 0. 001). Compared with GERD patients, IBS patients scored significantly lower on all SF-36 scales (P < 0.001) except physical functioning. Similarly, IBS patients had significantly worse HRQOL on selected SF-36 scales than patients with diabetes mellitus and ESRD. IBS patients had significantly better mental health SF-36 scale scores than patients with depression (P < 0.001). CONCLUSIONS: IBS patients experience significant impairment in HRQOL. Decrements in HRQOL are most pronounced in energy/fatigue, role limitations caused by physical health problems, bodily pain, and general health perceptions. These data offer further insight into the impact of IBS on patient functional status and well-being.     

Home collection for frequent HIV testing: acceptability of oral fluids, dried blood spots and telephone results. HIV Early Detection Study Group

OBJECTIVE: To assess the feasibility and acceptability of bimonthly home oral fluid (OF) and dried blood spot (DBS) collection for HIV testing among high-risk individuals. DESIGN: A total of 241 participants [including men who have sex with men (MSM), injecting drug users (IDU), and women at heterosexual risk] were recruited from a randomly selected subset of study participants enrolled at four sites in the HIV Network for Prevention Trials (HIVNET) cohort, and assigned at random to bimonthly home collection of OF or DBS specimens over a 6 month interval. Participants could select telephone calls or clinic visits to receive HIV test results. METHODS: Bimonthly specimens were tracked for adherence to the schedule, were evaluated for adequacy for testing, and tested using antibody assays and polymerase chain reaction (PCR) for DBS. The acceptability of bimonthly home OF and DBS collection and telephone counseling was assessed in an end-of-study questionnaire. RESULTS: The laboratory received 96 and 90% of expected OF and DBS specimens, respectively; 99% of each specimen type was adequate for testing. Almost all (95%) participants chose results disclosure by telephone. The majority of participants (85%) reported that bimonthly testing did not make them worry more about HIV, and almost all (98%) judged that with bimonthly testing their risk behavior remained the same (77%) or became less risky (21%). CONCLUSION: Bimonthly home specimen collection of both OF and DBS with telephone counseling is acceptable and feasible among study participants at high risk. These methods will be useful for the early detection of HIV infection and remote follow-up of research cohort participants in HIV vaccine and prevention trials.     

Perceptual responses in patients with inflammatory and functional bowel disease

BACKGROUND AND AIMS: Enhanced visceral sensitivity following a transient inflammatory process in the gut has been postulated as an aetiological mechanism of irritable bowel syndrome (IBS). In this study we compared perceptual responses to rectosigmoid distension in patients with mild chronic inflammation of the rectum (ulcerative colitis (UC)) and patients without mucosal inflammation (IBS) to determine if chronic low grade mucosal inflammation may be a plausible explanation for rectosigmoid hypersensitivity reported in both IBS and UC patients. METHODS: UC disease activity was quantified using activity index scores. Perception thresholds for discomfort during rectosigmoid distension were compared between 11 UC patients with quiescent or mild disease activity, 18 IBS patients, and 13 healthy controls. RESULTS: Although UC activity index scores negatively correlated with perceptual thresholds for discomfort (r=-0.76, p=0.016), UC patients had higher discomfort thresholds compared with IBS patients and controls before (p=0.02) and after (p<0.001) a noxious sigmoid conditioning stimulus. CONCLUSIONS: Rectal perception was attenuated in UC but enhanced in IBS. In chronic mild inflammation, activation of antinociceptive mechanisms may prevent the development of visceral hyperalgesia. Low grade mucosal inflammation alone is unlikely to be responsible for symptoms in functional gastrointestinal disorders.     

Endoscopic mucosal resection of early cancer and high-grade dysplasia in Barrett's esophagus

BACKGROUND & AIMS: In view of the mortality and morbidity rates of esophagectomy and the relatively large group of inoperable patients, local therapeutic techniques are required for high-grade dysplasia and early Barrett's cancer. METHODS: A prospective investigation of endoscopic mucosal resection was conducted in 64 patients (mean age, 65 +/- 10 years) who had early carcinoma (61 patients) or high-grade dysplasia (3 patients) in Barrett's esophagus. Thirty-five patients met the criteria for low risk: macroscopic types I, IIa, IIb, and IIc; lesion diameter up to 20 mm; mucosal lesion; and histological grades G1 and G2 and/or high-grade dysplasia (group A). The remaining 29 patients were included in group B (high risk). RESULTS: A total of 120 resections were performed, with no technical problems encountered. The mean number of treatment sessions per patient was 1. 3 +/- 0.6 in group A and 2.8 +/- 2.0 in group B (P < 0.0005). Only one major complication occurred, a case of spurting bleeding, which was managed endoscopically. Complete local remission was achieved significantly earlier (P = 0.008) in group A than in group B. In May 1999, complete remission had been achieved in 97% of the patients in group A and in 59% of those in group B; however, 1 patient in group A and 9 in group B are still undergoing treatment or awaiting the first check-up. During a mean follow-up of 12 +/- 8 months, recurrent or metachronous carcinomas were found in 14%. CONCLUSIONS: Endoscopic mucosal resection of early carcinoma in Barrett's esophagus is associated with promisingly low morbidity and mortality rates. The procedure may offer a new minimally invasive therapeutic alternative to esophagectomy, especially in low-risk situations. Comparisons with surgical results will need to be done when the long-term results of this procedure become available.     

Effekte von Ganzkörpervibrationen auf die neuromuskuläre Leistungsfähigkeit von Frauen über dem 65. Lebensjahr

Sarcopenia is linked to an increased risk of morbidity and mortality in the aging. Whole body vibration (WBV) exercises are currently discussed as a “gentle” alternative to conventional exercises to improve muscle mass. The present study scrutinized whether a multipurpose (exercise) training program using WBV can improve muscle mass and neuromuscular capacity, while lowering fall risk. A total of 151 postmenopausal women were randomized into three groups: exercise group (TG), exercise group with vibration (VTG), and fitness control group (CG). The TG group participated in an exercise program including leg strengthening training twice a week over 12 months, while the VTG carried out an identical program with the leg exercises performed under WBV. Despite a positive trend regarding lean body mass in the two exercise groups, there was no difference between groups. Both exercise groups showed a significant increase (vs. KG) in trunk strength. An improvement in both exercise groups was also measured with respect to leg strength, but only the VTG showed significant differences compared to the CG. In addition, a significant lower risk of falls compared with the CG was evident only in VTG.     

Management of urethral catheter knot in a neonate

To accommodate the small size of the infant urethra, finer, more flexible tubes are often used for urinary catheterization in the pediatric intensive care units. These tubes have the ability to knot in the bladder, occasionally requiring surgical removal. The mechanism of knotting appears to result from excessive intravesical catheter coiling, and as the bladder decompresses the catheter tip can migrate through a coil thereby creating a knot. Review of the literature from 1975 to 2000 identified 19 cases of urethral catheter knotting in the pediatric bladder with two reports of prostatic urethral involvement. Herein, we describe the first reported instance of catheter knotting within the penile urethra and describe the surgical technique employed for its removal.