The importance of pulmonary venous flow measurement for evaluating left ventricular end-diastolic pressure in patients with coronary artery disease in the early stage of diastolic dysfunction.

Transmitral flow pattern assessed by pulsed Doppler echocardiography is widely used to evaluate left ventricular end-diastolic pressure (LVEDP). A restrictive mitral flow pattern is well recognized as a finding of severely elevated LVEDP. On the other hand, an abnormal relaxation pattern can be interpreted many ways. For example, some patients who display an abnormal relaxation pattern have a mild impairment of left ventricular (LV) relaxation as a result of aging, and others have severely impaired LV diastolic function. To evaluate LVEDP in patients with abnormal relaxation mitral filling patterns, we studied 55 patients who had coronary artery disease with abnormal relaxation pattern who underwent elective cardiac catheterization. We recorded the transmitral and pulmonary venous flow velocity curves and measured the duration of the mitral A wave (MAd) and pulmonary venous reversal wave during atrial contraction (PAd). Positive correlations were found between PAd and LVEDP (r = 0.65, P <.01) and between PAd-MAd and LVEDP (r = 0.7, P <.0001); however, MAd was not significantly correlated with LVEDP. In conclusion, PAd must be measured for an accurate evaluation of LV end-diastolic pressure in patients with an abnormal relaxation pattern in the transmitral flow velocity curve.     

Immunomodulatory effects of stem cells

Adult‐derived mesenchymal stem cells have received considerable attention over the past two decades for their potential use in tissue engineering, principally because of their potential to differentiate into multiple stromal‐cell lineages. Recently, the immunomodulatory properties of mesenchymal stem cells have attracted interest as a unique property of these cells that may be harnessed for novel therapeutic approaches in immune‐mediated diseases. Mesenchymal stem cells have been shown to inhibit the proliferation of activated T‐cells both in vitro and in vivo but to stimulate T‐regulatory cell proliferation. Mesenchymal stem cells are also known to be weakly immunogenic and to exert immunosuppressive effects on B‐cells, natural killer cells, dendritic cells and neutrophils through various mechanisms. Furthermore, intravenous administration of allogeneic mesenchymal stem cells has shown a marked suppression of host immune reactions in preclinical animal models of large‐organ transplant rejection and in various autoimmune‐ and inflammatory‐based diseases. Some clinical trials utilizing human mesenchymal stem cells have also produced promising outcomes in patients with graft‐vs.‐host disease and autoimmune diseases. Mesenchymal stem cells identified from various dental tissues, including periodontal ligament stem cells, also possess multipotent and immunomodulatory properties. Hence, dental mesenchymal stem cells may represent an alternate cell source, not only for tissue regeneration but also as therapies for autoimmune‐ and inflammatory‐mediated diseases. These findings have elicited interest in dental tissue mesenchymal stem cells as alternative cell sources for modulating alloreactivity during tissue regeneration following transplantation into human leukocyte antigen‐mismatched donors. To examine this potential in periodontal regeneration, future work will need to assess the capacity of allogeneic periodontal ligament stem cells to regenerate periodontal ligament in animal models of periodontal disease. The present review describes the immunosuppressive effects of mesenchymal stem cells on various types of immune cells, the potential mechanisms through which they exert their mode of action and the preclinical animal studies and human clinical trials that have utilized mesenchymal stem cells, including those populations originating from dental structures.     

Changes in urinary NTX levels in patients with primary osteoporosis undergoing long-term bisphosphonate treatment

BACKGROUND: Bisphosphonates, antiresorptive drugs, are widely used to treat osteoporosis patients. However, recent reports indicated that several osteoporosis patients who underwent long-term bisphosphonate therapy subsequently developed severe suppression of bone turnover. We investigated whether urinary crosslinked N-telopeptide of type I collagen (NTX), a bone resorption marker, in osteoporosis patients was highly suppressed during long-term treatment with alendronate or risedronate. METHODS: We investigated 87 primary osteoporosis outpatients who were treated with alendronate or risedronate for more than 2 years. All patients were women, with an average age of 72.6 years. Altogether, 49 patients were treated with alendronate and 38 with risedronate, and the average administration period was 3.5 years. We defined high suppression as NTX being reduced <9.3 nmol bone collagen equivalent/mmol.Cr and a 35% decrease from baseline. RESULTS: In total, 11 of 87 patients (12.6%) had high NTX suppression based on the above criteria. The incidences of high suppression of NTX at 1,2,3,and 4 years after starting the treatment were 0%, 1.1%, 11.9%, and 4.7%, respectively. The average age, bone mineral density, and NTX values at baseline and the administration period were not associated with high suppression of NTX during alendronate or risedronate treatment. Regarding suppression of NTX during long-term treatment, there was no significant difference between alendronate and risedronate. CONCLUSIONS: The results suggested that long-term treatment with bisphosphonates necessitates careful follow-up of the patients.     

Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ): part 4. Establishment of equations for severity scores

Background To establish a patient-oriented outcome measure for cervical myelopathy, a subcommittee of the Japanese Orthopaedic Association (JOA) developed a new scoring system to evaluate the overall clinical status of patients, which could be completed by patients themselves. The subcommittee completed three large-scale studies to select and modify questions derived from various preexisting outcome measures including Short Form-36, and then finalized and validated the questionnaire, which comprised 24 questions. Methods The finalized questionnaire was administered to 369 patients with cervical myelopathy due to disc herniation, spondylosis, or ossification of posterior longitudinal ligament by randomly selected board-certified spine surgeons. Patients with different severities of myelopathy were included to insure accuracy and responsiveness of this questionnaire against patients’ different neurological status. Results Data of 236 patients were employed and were subjected to rigorous statistical analyses. There was no question that was difficult to answer and distribution of answers for each question was not concentrated to one choice, indicating the appropriateness of all 24 questions. Results of factor analysis suggested that the 24 questions could be divided into five different factors or functional domains. The factors were defined as follows: factor 1, lower extremity function; factor 2, quality of life; factor 3, cervical spine function; factor 4, bladder function; and factor 5, upper extremity function. Finally, equations that would yield scores for the five factors were assembled. The score to be used to represent the degree of patients’ disability or status in each domain can be calculated by multiplying prefixed numbers of selected answers to questions by preassigned coefficients. Coefficients were defined to make the minimum score 0 and the maximum score 100. Conclusions We have successfully established a questionnaire that is able to demonstrate the status of patients suffering cervical myelopathy from five different aspects represented by five intuitive numerical scores. The final issue to be confirmed is the responsiveness of this questionnaire to changes in patients’ status after various surgical and nonsurgical treatments.     

Comparative study of direct polymerase chain reaction, microscopic examination and culture-based morphological methods for detection and identification of dermatophytes in nail and skin samples

The positive rates of dermatophytes isolated and identified by conventional methods are rather low. Moreover, clinical isolates sometimes show atypical morphology, and in such cases microscopic methods are not applicable for identification. The present study was performed to assess the utility of specific polymerase chain reaction (PCR)-based methods for Trichophyton rubrum and Trichophyton mentagrophytes as diagnostic tools for dermatophytoses. Both conventional morphological identification and specific PCR methods based on the nuclear ribosomal internal transcribed spacer (ITS)1 DNA sequence were performed to identify dermatophyte species from clinical specimens of patients who visited Kawasaki Social Insurance Hospital between 16 May and 17 August 2005. Specific PCR methods were also directly applied to clinical specimens, and the results of the two methods were compared. The clinical samples examined consisted of 126 skin scale specimens and 80 nail specimens. The positive rates of culture isolation from clinical specimens were 67% and 33% for skin scale and nail specimens, respectively. In contrast, PCR analysis yielded a positive rate of 100% for clinical isolates from both skin scales and nails, and rates of 95% and 99% were obtained by direct application to clinical specimens. The results of the present study indicated that specific PCR is highly advantageous as a diagnostic tool for detection and identification of dermatophytes on direct application to skin scale or nail specimens.     

Strategy for retreatment of therapeutic failure of eradication of Helicobacter pylori infection

BACKGROUND AND AIM: A proton pump inhibitor (PPI)-based triple therapy consisting of a PPI, amoxicillin (A) and clarithromycin (C) or metronidazole (M) provides an eradication rate ranging from 80 to 90%. However, there have been few controlled studies with regard to the most effective regimen to re-treat patients after failure of the first-line therapy. Accordingly, we retrospectively reviewed our experiences and compared regimens with different combinations of antimicrobials to determine the optimal retreatment regimen. METHODS: Out of 133 patients who had received second-line therapy after failure of first-line PPI/AC therapy, we selected, for review, patients who took the prescribed drugs for first-line therapy equal to, or more than 80%. As a result, data on 114 patients (83 males and 31 females; mean age 49.1 +/- 13.0 years; peptic ulcer n = 89; non-ulcer dyspepsia, n = 25) were eligible for evaluation. They had either repeated the PPI/AC regimen (n = 34; 5-14 days), or had been administered the PPI/AM regimen (n = 80; 10 days). The cure rates of the two regimens were compared. RESULTS: The eradication rates for second-line therapy with the PPI/AC regimen versus the PPI/AM regimen were 52.9% (95% CI, 35-70) versus 81.3% (95% CI, 71-89) by intention-to-treat analysis (P < 0.01), and 62.1% (95% CI, 42-79) versus 91.4% (95% CI, 81-97) by per-protocol analysis (P < 0.01). CONCLUSION: The eradication rate for the PPI/AM retreatment regimen was significantly higher than for the repeated PPI/AC regimen, suggesting that a 10-day PPI/AM regimen can be recommended as a retreatment regimen for patients who had first-line eradication therapy by PPI/AC regimens.     

Angiotensin(1-7) potentiates bradykinin-induced vasodilatation in man.

BACKGROUND: It has been clearly demonstrated that angiotensin(1-7) potentiates the vasodilating effect of bradykinin in isolated vessels of animals. OBJECTIVE: To investigate the interaction between angiotensin(1-7) Ang(1-7) and bradykinin in human forearm resistant vessels of normotensive healthy men in vivo, by the measurement of forearm blood flow using venous occlusion, strain-gauge plethysmography with intra-arterial infusions of peptides in a placebo-controlled, double-blind, cross-over design. METHODS: In eight men, bradykinin was infused intra-arterially twice; placebo, Ang(1-7), or angiotensin II was co-infused with the second infusion. The effect of inhibition of nitric oxide synthase on the interaction between Ang(1-7) and bradykinin was also tested in eight other individuals. The effects of Ang(1-7) were analyzed by analysis of variance (ANOVA) and by the ratios of individually derived areas under the dose-response curves (AUC) of bradykinin, adjusted for changes in the AUCs by repeated infusions of bradykinin with placebo. RESULTS: Ang(1-7) (1000 pmol/min) significantly potentiated the vasodilating effect of bradykinin compared with the effect of saline (P = 0.0471, ANOVA) and in a dose-dependent manner (adjusted AUC ratio [95% confidence interval (CI)] 2.75 (1.72 to 3.78) with 1000 pmol/min, 1.62 (1.31 to 1.93) with 100 pmol/min, and 0.98 (0.80, to 1.09) with 10 pmol/min). This effect was completely abolished by co-infusion of NG-monomethyl-l-arginine [AUC ratio 0.98 (0.90 to 1.04)]. Ang(1-7) did not affect the vasodilating effects of either acetylcholine or sodium nitroprusside. CONCLUSIONS: Ang(1-7) potentiates the vasodilating effect of bradykinin, possibly through a mechanism(s) involving nitric oxide release, in human forearm resistance vessels.     

A clinical study of associated bladder cancer in patients with renal pelvic and ureteral cancer]

Retrospective study on the frequency of associated bladder cancer and the influence on the prognosis was carried out in 170 cases of renal pelvic and ureteral cancer. The number of cases of associated bladder cancer coexistent with renal pelvic and ureteral cancer was 31 (18.2%), and the number of subsequent cases 3 (19.4%). The frequency of occurrence of the primary tumor site was 27.2% in the renal pelvis, 45.6% in the ureter and 58.3% in both renal pelvis and ureter. Multiple tumors occurring in the renal pelvis and ureter occupy a high percentage. As for the degree of differentiation, many cases were subsequent to G1. As for the stage, a few cases with bladder cancer were subsequent to T4, but there was no definite tendency in the occurrence of bladder cancer. The prognosis of renal pelvic and ureteral cancer: the 10-year survival rate was 93.3% for G1, 66.6% for G2 and 12.4% for G3. As can be seen, there was good correlation with the pathological gradings. It must be remembered, however, that 5-year survival rates in cases of associated bladder cancer of coexistent type, in cases of subsequent type and in cases without associated bladder cancer were 56.2%, 72.7% and 64.8%, respectively: there was no significant difference. Bladder cancer associated with renal pelvic and ureteral cancer makes the therapy troublesome, but no influence on the prognosis was observed. Therapy in conformity with the pathological grading and stage is regarded as particularly important in cases of associated bladder cancer.     

Retropharyngeal rhabdomyosarcoma mimicking pseudotumor cerebri.

A 6-year-old male presented with headache, vomiting, visual obscuration, and papilledema. Clinical presentation, initial laboratory data, and radiologic evaluation suggested a diagnosis of pseudotumor cerebri. The development of lower cranial nerve palsies after transient resolution of symptoms prompted reassessment of the diagnosis, which revealed retropharyngeal rhabdomyosarcoma involving the right jugular vein. Cerebral angiography demonstrated the complete venous occlusion at the jugular foramen. Careful neurologic follow-up is essential in a patient with pseudotumor cerebri or idiopathic intracranial hypertension.     

A randomized phase III trial of adjuvant chemotherapy with UFT for completely resected pathological stage I non-small-cell lung cancer: the West Japan Study Group for Lung Cancer Surgery (WJSG)--the 4th study.

PURPOSE: To examine the efficacy of UFT, an oral 5-fluorouracil derivative agent, as post-operative adjuvant therapy for pathologic (p-) stage I non-small-cell lung cancer (NSCLC), because a previous randomized study had suggested it was efficacious for early-stage NSCLC patients. PATIENTS AND METHODS: Patients with completely resected p-stage I, adenocarcinoma or squamous cell carcinoma were eligible. A total of 332 patients were randomized to the surgery-alone group (control group) and the treatment group (UFT 400 mg/m(2) for 1 year after surgery, UFT group) after stratification by the histologic types. RESULTS: For all patients, the 5- and 8-year survival rates for the UFT group were 82.2% and 73.0%, and those for the control group were 75.9% and 61.2%, respectively; no statistically significant improvement of survival was achieved by UFT administration (P=0.105). For Ad patients, the 5- and 8-year survival rates of the UFT group (n=120) were 85.2% and 79.5%, respectively, which seemed better than those of the control group (n=121) (79.2% and 64.0%, respectively; P=0.081). For squamous cell carcinoma patients, there was also no difference in survival between the control group (n=48) and the UFT group (n=43) (P=0.762). For all pT1 patients, the 5- and 8-year survival rates of the UFT group were 83.6% and 82.1%, respectively, significantly better than those of the control group (77.9% and 57.6%, respectively, P=0.036); UFT was not significantly effective for pT2 patients. For pT1 adenocarcinoma patients, UFT administration markedly improved the survival (P=0.011). CONCLUSION: Post-operative UFT administration did not significantly improve post-operative survival of p-stage I NSCLC patients. Subset analyses suggested that UFT might be effective in pT1N0M0 adenocarcinoma patients.