Downbeat positioning nystagmus is a common clinical feature despite variable phenotypes in an FHM1 family

Clinical examinations and mutational analyses were carried out in three patients of a Japanese familial hemiplegic migraine (FHM) pedigree. Each affected member demonstrated a broad clinical spectrum that included hemiplegic migraine with progressive cerebellar ataxia, migraine without aura, and episodic ataxia. Despite this variability, all members exhibited marked downbeat positioning nystagmus, and magnetic resonance images (MRI) all showed cerebellar atrophy predominantly of the cerebellar vermis. All affected members had a T666M missense mutation in the protein encoded by the CACNA1A gene (calcium channel, voltage-dependent, P/Q type, alpha 1A subunit). Although clinical features associated with the T666M CACNA1A mutation are highly variable, downbeat positioning nystagmus may be an important clinical feature of this disease.     

Fractional anisotropy values detect pyramidal tract involvement in multiple system atrophy

OBJECTIVE: Pathological studies have shown remarkable pyramidal tract involvement in multiple system atrophy (MSA), while clinical pyramidal signs are relatively rare. We investigated the fractional anisotropy (FA) values to assess the degree of pyramidal tract involvement in MSA, in comparison with amyotrophic lateral sclerosis (ALS) and controls. Furthermore, we compared FA values between MSA patients with or without clinical pyramidal signs and controls, and between MSA patients with or without positive conventional MRI findings and controls. METHODS: We evaluated FA values in the internal capsule, corona radiate and whole pyramidal tract using visualized tractography of 65 subjects (20 probable MSA patients, 28 age-matched ALS patients, and 17 age-matched healthy controls) using a 3.0T magnetic resonance system. RESULTS: The FA values in the internal capsule, corona radiate, and whole pyramidal tract were significantly lower in MSA patients than in controls and were at a level similar to those of ALS patients. In addition, low FA values were prominent in MSA patients, even in those with short duration of illness, lacking precentral gyrus hyperintensity in FLAIR images, and without pyramidal signs. CONCLUSION: FA values could identify pyramidal tract degeneration even in patients with early phase MSA and those without clinical pyramidal signs or abnormal MRI findings. More extensive degeneration of the pyramidal tract occurs in MSA than so far believed.     

Long-term control or possible cure? Treatment of stage D2 prostate cancer under chemotherapy using cisplatin and estramustine phosphate followed by maximal androgen blockade

Metastatic prostate cancer (PC) is incurable by androgen deprivation therapy alone, due to the presence of androgen-independent/supersensitive cells in hormone-naive PC. A 67-year-old man was diagnosed with PC (Gleason score, 5 + 4) with multiple bone metastases. He was treated by chemohormonal therapy with cisplatin and estramustine phosphate (EMP) followed by maximal androgen blockade, and showed a complete response. As of the time of writing, no clinical or prostate-specific antigen recurrence has been observed for over 15 years, despite cessation of the treatment. This is the first report to indicate a possible cure of metastatic PC by chemohormonal therapy combined with appropriate anti-tumor drugs targeted to both androgen-independent and -dependent clones before the hormone-refractory state.     

The Potential for Essential Trauma Care to Empower Communities and Tackle Inequities

In an attempt to address rapidly increasing injuries in low-income and middle-income countries (LMICs), the Essential Trauma Care Project was started with the goal of standardizing trauma care systems. This project, although part of "vertical" essential health services, has the potential to strengthen the health care system as a whole and to empower communities. Improved diagnosis, triage, referral, communication, and transport benefit the integrated health care systems weakened by vertical approaches. This project mobilizes existing resources, including lay people, to establish a "local model of prehospital care," which can raise community capability and foster trust in health systems. This article describes how this project can be an intersection between vertical and horizontal approaches.     

C4d deposition and cellular infiltrates as markers of acute rejection in rat models of orthotopic lung transplantation

BACKGROUND: C4d is a useful marker of antibody-mediated rejection in cardiac and renal transplants, but clinical studies examining correlations between circulating alloantibodies, C4d deposition, and rejection in lung transplants have yielded conflicting results. METHODS: We studied circulating alloantibody levels and C4d deposition in two rat models of lung transplantation: Brown Norway (BN) to Wistar-Kyoto (WKY) and PVG.R8 to PVG.1U lung allografts. The availability of C6 deficient (C6-) and C6 sufficient (C6+) PVG 1U rats allowed evaluation of the effects of the terminal complement components on graft injury and C4d deposition. RESULTS: The lung allografts had histologic features resembling human posttransplant capillaritis, characterized by neutrophilic infiltration of alveoli, edema, and hemorrhage. Immunoperoxidase stains on cross sections of allografts showed intense, diffuse, C4d deposition in a continuous linear pattern on the vascular endothelium. C4d deposits were found in both BN to WKY and PVG R8 to 1U allografts, whereas no staining was detectable in WKY to WKY isografts or native lungs. Complement deposition was associated with vascular disruption in C6+, but not in C6- recipients. The presence of circulating donor-specific alloantibodies was verified by flow cytometry. Cell-specific staining revealed perivascular accumulation of macrophages and T lymphocytes whereas neutrophils were sequestered in the intravascular and alveolar capillary compartments. CONCLUSIONS: The deposition of C4d on vascular endothelium as well as the coincident presence of alloantibodies is consistent with previous findings in antibody-mediated rejection of renal and cardiac transplants. Furthermore, the histological features of our allografts support the concept that posttransplant capillaritis is a form of humoral rejection.     

Long-Term Characteristics of 5-Year Survivors After Liver Resection for Colorectal Metastases

Background We investigated factors affecting 5-year survival in patients undergoing hepatic resection for colorectal cancer metastases, including events long after initial hepatectomy. Although retrospective studies have demonstrated survival benefit of hepatectomy for metastatic colorectal cancer, few have included sufficient 5-year survivors to identify survival-related factors throughout the clinical course. Methods We divided 156 patients with hepatectomy for colorectal cancer metastases into 5-year survivors (n = 64) and patients dying before 5 years after hepatectomy (n = 92). Clinicopathologic data were compared retrospectively with respect to long-term outcome. Results By multivariate analysis, large liver tumors (adjusted relative risk, 2.029; P = .011), short tumor doubling time (1.809; P = .026), and origin from poorly differentiated primary adenocarcinoma (12.632; P = .001) compromised survival, whereas initial treatment-related variables did not. Although no difference was seen in initial treatment-related variables between 5-year survivors with recurrence after hepatectomy and patients dying before 5 years, repeat surgery was used more frequently in survivors (P < .001), typically with adjuvant chemotherapy. Conclusions Reoperations for each recurrence of metastases, followed by additional chemotherapy, frequently resulted in long survival.     

Increased preoperative serum C-reactive protein level predicts a poor prognosis in patients with localized renal cell carcinoma

OBJECTIVE: To evaluate the value of the preoperative serum C-reactive protein (CRP) level in the prognosis of patients with localized renal cell carcinoma (RCC). PATIENTS AND METHODS: The study comprised 101 patients who had a radical nephrectomy for localized RCC (pT1-3N0M0). An elevated CRP was defined as >0.5 mg/dL before surgery. Survival rates for each variant were calculated using the Kaplan-Meier method, with the difference between survival curves evaluated using the log-rank test. Multivariate analysis was by Cox proportional hazard model; for all analyses the difference was considered significant when P < 0.05. RESULTS: The median (range) follow-up was 55 (2-187) months; 26 patients (26%) had high CRP levels, and 12 (46%) of these and three (4.0%) of the remaining 75 died from disease. The 5- and 10-year disease-specific survival rates (75% and 30%, respectively) in patients with high CRP levels were significantly worse than those in patients with normal CRP levels (both 93%, P < 0.001). In other variants, preoperative haemoglobin concentration, pathological stage, grade, histological type and microvascular tumour invasion were also related to disease-specific survival. By the Cox proportional hazards model, pathological stage and an elevated CRP were the most important prognostic factors for disease-specific survival in patients with localized RCC (P = 0.008 and 0.012, respectively). CONCLUSION: The preoperative CRP level was associated with poor survival in patients with localized RCC.