Dural infolding during C1-2 myelography

Inward buckling of the dura at C1-2 may occasionally occur with hyperextension of the neck and can result in a difficult or unsuccessful puncture when the posterior lateral C1-2 approach is used for cervical myelography. In this circumstance, placement of the head in a neutral or slightly flexed position may widen the posterior subarachnoid space and facilitate the needle puncture.     

Stage I seminoma and carboplatin risks

Should the report of carboplatin morbidity by Powles et al.[1] in this issue influence the management of patients withstage I seminoma post-orchidectomy? In a study of 199 patientstreated with one or two cycles of adjuvant carboplatin as asingle agent, and followed for between 0.1 and 20.1 years (median9), the analysis showed no excess mortality compared with theage and sex-matched UK population with 95% confidence intervals(CIs) on their standardised mortality ratio (SMR) from 0.36to 1.83.     

Orchidectomy alone for stage I seminoma of the testis

Between 1983 and 1988, 113 patients with Stage I seminoma were managed after orchidectomy by surveillance rather than adjuvant radiotherapy. The actuarial risk of relapse at 3 years was 15.8% (95% confidence interval, 7.8% to 23.8%). All 13 patients who experienced a relapse are currently in remission (4 to 45 months after salvage therapy), although 5 suffered second relapses requiring further treatment. Close surveillance is a safe alternative to adjuvant radiotherapy in Stage I seminoma. However, the policy requires prolonged observation of patients with intensive use of resources. Therefore, adjuvant radiotherapy should be considered the treatment of choice.     

生殖腺及生殖腺外畸胎瘤的超声诊断

目的；探讨超声对各部位畸胎瘤的诊断价值。方法：对42例经手术及病理证实的畸胎瘤与超声检查结果对照，并回顾分析其声像特征。结果：畸胎瘤具有一些特征性声像图表现，其肿块检出率100％，诊断符合率89．8％，其中生殖腺畸瘤诊断符合率96．8％，生殖腺外畸胎瘤诊断符合率82．0％。结论：畸胎瘤的超声诊断符合率较高，应为目前首选检查方法。少见部位畸胎瘤因认识不足易造成误诊，良恶性的鉴别亦存在误差。     

Disulfide formation as a probe of folding in GroEL-GroES reveals correct formation of long-range bonds and editing of incorrect short-range ones

The chaperonin GroEL assists protein folding by binding nonnative forms through exposed hydrophobic surfaces in an open ring and mediating productive folding in an encapsulated hydrophilic chamber formed when it binds GroES. Little is known about the topology of nonnative proteins during folding inside the GroEL-GroES cis chamber. Here, we have monitored topology employing disulfide bond formation of a secretory protein, trypsinogen (TG), that behaves in vitro as a stringent, GroEL-GroES-requiring substrate. Inside the long-lived cis chamber formed by SR1, a single-ring version of GroEL, complexed with GroES, we observed an ordered formation of disulfide bonds. First, short-range disulfides relative to the primary structure formed, both native and nonnative. Next, the two long-range native disulfides that "pin" the two beta-barrel domains together formed. Notably, no long-range nonnative bonds were ever observed, suggesting that a native-like long-range topology is favored. At both this time and later, however, the formation of several medium-range nonnative bonds mapping to one of the beta-barrels was observed, reflecting that the population of local nonnative structure can occur even within the cis cavity. Yet both these and the short-range nonnative bonds were ultimately "edited" to native, as evidenced by the nearly complete recovery of native TG. We conclude that folding in the GroEL-GroES cavity can favor the formation of a native-like topology, here involving the proper apposition of the two domains of TG; but it also involves an ATP-independent conformational "editing" of locally incorrect structures produced during the dwell time in the cis cavity.     

DFNB74, a novel autosomal recessive nonsyndromic hearing impairment locus on chromosome 12q14.2-q15

Autosomal recessive nonsyndromic hearing impairment (ARNSHI) segregating in three unrelated, large consanguineous Pakistani families (PKDF528, PKDF859 and PKDF326) is linked to markers on chromosome 12q14.2-q15. This novel locus is designated DFNB74 . Maximum two-point limit of detection (LOD) scores of 5.6, 5.7 and 2.6 were estimated for markers D 12 S 313, D 12 S 83 and D 12 S 75 at θ = 0 for recessive deafness segregating in these three families. Haplotype analyses identified a critical linkage interval of 5.35 cM (5.36 Mb) defined by D 12 S 329 at 74.58 cM and D 12 S 313 at 79.93 cM. DFNB74 is the second ARNSHI locus mapped to chromosome 12, but the physical intervals do not overlap with one another. A locus contributing to the early onset, rapidly progressing hearing loss of A/J mice ( ahl4 , age-related hearing loss 4) was reported to map to chromosome 10 in a region of conserved synteny to DFNB74 , suggesting that ahl4 and DFNB74 may be due to mutations of the same gene in these two species.     

Prostate-specific antigen velocity in untreated, localized prostate cancer

OBJECTIVE

To report the results of a prospective study of active surveillance of untreated prostate cancer, with a focus on baseline predictors of prostate‐specific antigen (PSA) velocity, as PSA velocity before treatment is an important predictor of prostate cancer mortality, and patients on active surveillance are monitored for several years to estimate the PSA velocity and thus select patients for radical treatment.

PATIENTS AND METHODS

A prospective study of active surveillance for localized prostate cancer opened at the Royal Marsden Hospital in 2002. Eligible patients had clinical stage T1/T2a, N0/Nx, M0/Mx adenocarcinoma of the prostate with a serum PSA level of <15 ng/mL, a Gleason score of ≤7 with primary grade ≤3, and less than half the biopsy cores positive. The PSA velocity before treatment was analysed in relation to baseline clinical characteristics.

RESULTS

In all, 237 patients on surveillance were followed for a median of 24 months (median age 67 years; median initial PSA level 6.5 ng/mL; median pretreatment PSA velocity 0.44 ng/mL per year). On multivariate analysis, PSA density (i.e. serum PSA level/prostate volume) was the only significant determinant of PSA velocity (P < 0.001). Patients with a PSA density above or below the median (0.185 ng/mL/mL) had a median (interquartile range) PSA velocity of 0.92 (0.34–1.77) ng/mL per year and 0.35 (? 0.06, 0.80) ng/mL per year, respectively.

CONCLUSIONS

PSA density, which is readily available at the time of diagnosis, is an independent determinant of PSA velocity in untreated, localized prostate cancer. If this is confirmed, PSA density could be used to inform the often difficult choice between active surveillance and immediate radical treatment.