Three cases of neonatal herpes simplex virus infection presenting as fulminant hepatitis

We report three cases of neonatal herpes simplex virus (HSV) infection presenting as fulminant hepatitis. None of the patients had clear risk factors for HSV infection and they all died. Antiviral treatment for HSV is currently available but must be administered early in the course of the disease before irreversible liver tissue damage is present. Since the diagnosis may be difficult to establish, we wish to draw the attention of clinicians to the presentation of neonatal HSV infection and suggest that in such cases viral cultures, including culture of liver tissue, should be obtained early and antiviral treatment administered while awaiting the culture results.     

Construction noise: exposure,effects, and the potential for remediation; a review and analysis

More than one-half million construction workers are exposed to potentially hazardous levels of noise, yet federal and state Occupational Safety and Health Administration (OSHA) programs provide little incentive to protect them against noise-induced hearing loss. Construction noise regulations lack the specificity of general industry noise regulations. In addition, problems that characterize the construction industry, such as worker mobility and the large proportion of small businesses, make implementing hearing conservation measures more difficult. The apparent severity of exposure depends greatly on the measurement method, with the 3-dB exchange rate almost always showing higher average exposure levels than the 5-dB (OSHA) rule. Construction workers demonstrate hearing threshold levels that generally conform to those expected in manufacturing. The prevalence of hearing protection device (HPD) use among U.S. construction workers is very poor, partly because of perceived difficulties in hearing and understanding speech communication and warning signals. In addition, masking by noise of necessary communication and warning signals is of particular concern in construction, where recent research demonstrated the association between fatalities and the failure to hear reverse alarms. Judicial use of HPDs is of the utmost importance, along with avoiding overattenuation, selecting HPDs with uniform attenuation, and using noise-attenuating communication systems when possible. A successful hearing conservation program in British Columbia can serve as a model for the United States, with a long-standing positive safety culture, a high percentage of HPD use, improvement in average hearing threshold levels over the last decade, and a centralized record-keeping procedure, which helps solve the problem of worker mobility. However, controlling construction noise at the source is the most reliable way to protect worker hearing. U.S. manufacturers and contractors should benefit from the activities of the European Community, where noise control and product labeling in construction has been carried out for more than 20 years.     

Membrane association of myotubularin-related protein 2 is mediated by a pleckstrin homology-GRAM domain and a coiled-coil dimerization module

Mutations in the myotubularin (MTM)-related protein 2 (MTMR2) gene are responsible for the severe autosomal recessive neuropathy Charcot-Marie-Tooth disease type 4B1. MTMR2 belongs to the MTM family of dual-specific phosphatases that use phosphatidylinositol (PI) 3,5-bisphosphate [PI(3,5)P2] and PI 3-phosphate [PI(3)P] as their substrate. Because these substrates are localized in the membrane bilayer, membrane targeting of Mtmr2 is an important regulatory mechanism. In hypoosmotically stressed COS cells with increased levels of PI(3,5)P2, Mtmr2 is bound to the membrane of vacuoles formed under these conditions. Using several mutant forms of Mtmr2, we identified two domains that are necessary for membrane association: (i) A pleckstrin homology-GRAM domain; and (ii) a coiled-coil module. Protein-lipid overlay assays show that the pleckstrin homology-GRAM domain binds to PI(3,5)P2 and PI(5)P, a substrate and a product of the Mtmr2 enzyme, respectively. We also demonstrate that Mtmr2 forms a dimer and that the C-terminal coiled-coil is responsible for homodimerization, in addition to membrane association. Our data indicate that phosphoinositide-protein interactions, as well as protein-protein interactions, are necessary for the correct regulation of MTMR2.     

Identification of the regulatory region of the peripheral myelin protein 22 (PMP22) gene that directs temporal and spatial expression in development and regeneration of peripheral nerves

Minor changes in PMP22 gene dosage have profound effects on the development and maintenance of peripheral nerves. This is evident from the genetic disease mechanisms in Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) as well as transgenic animals with altered PMP22 gene dosage. Thus, regulation of PMP22 is a crucial aspect in understanding the function of this protein in health and disease. In this study, we have generated transgenic mice containing 10 kb of the 5'-flanking region of the PMP22 gene, including the two previously identified alternative promoters, fused to a lacZ reporter gene. We show that this part of the PMP22 gene contains the necessary information to mirror the endogenous expression pattern in peripheral nerves during development and regeneration and in mouse models of demyelination due to genetic lesions. Transgene expression is strongly regulated during myelination, demyelination, and remyelination in Schwann cells, demonstrating the crucial influence of neuron-Schwann cell interactions in the regulation of PMP22. In addition, the region of the PMP22 gene present on this transgene confers also neuronal expression in sensory and motor neurons. These results provide the crucial basis for further dissection of the elements that direct the temporal and spatial regulation of the PMP22 gene and to elucidate the molecular basis of the master program regulating peripheral nerve myelination.     

Postoperative pulmonary dysfunction after bilateral inguinal hernia repair: a prospective randomized study comparing the Stoppa procedure with laparoscopic total extraperitoneal repair (TEPP)

The infraumbilical incision required for open repair of bilateral inguinal hernia with a giant prosthesis is associated with postoperative pain and respiratory impairment. The aim of this study was to evaluate the postoperative respiratory dysfunction after bilateral hernia surgery. Thirty-nine patients were randomized into two groups: open repair according to the Stoppa technique and laparoscopic extraperitoneal repair (TEPP). Respiratory function tests were performed before and 24 hours after surgery. The two groups were well matched for age, American Society of Anesthesiologists (ASA) risk score, type of hernia, and preoperative lung function. The postoperative forced vital capacity (FVC), peak expiratory flow (PEF), and forced expiratory volume in 1 second (FEV 1.0) were significantly altered in both groups. The PEF dropped 15% in both groups. The FVC dropped 22% after Stoppa versus 25% after laparoscopy (P = 0.7). The FEV 1.0 dropped 21% after Stoppa versus 9% after laparoscopy (P = 0.12). We conclude that laparoscopic preperitoneal and open bilateral hernia repair are followed by similar ventilatory dysfunction, although a trend toward better postoperative FEV 1.0 was noted after laparoscopy. This might play a role in selected patients with severe pulmonary limitations. Overall, the limited drop in pulmonary function following bilateral hernia repair under general anesthesia may serve to explain the low pulmonary morbidity that follows these procedures.     

Does muscle inhibition after knee injury increase the risk of osteoarthritis?

Knee pathologies are commonly associated with muscle inhibition, an inability to fully activate the knee extensors during voluntary contractions. This inhibition results in knee extensor weakness, and is thought to limit the functional recovery of the knee joint structures. The possible contribution of persistent knee extensor inhibition to osteoarthritis is discussed.     

软X线治疗皮肤基底细胞癌和鳞状细胞癌

背景：作者制定了一个应用软X线治疗表皮恶性肿瘤的计划，该计划虑及临床已诊断的肿瘤在治疗下的退化现象。目标：根据治愈率和后期溃疡形成来评价本计划的有效性。方法：对1988-1992年间接受连续照射的1267例基底细胞癌和鳞状细胞癌患者进行随访（平均随访77个月）。结果：肿瘤复发率5．1％，与其大小、厚度及时间-剂量分次因子有关。溃疡形成率6．3％，取决于照射野大小、X线的硬度，在一个较小照射野（直径≤4cm）内则与总的照射剂量和时间-剂量分次因子有关。82．5％的溃疡能适当治愈。局限性：尚无证据表明本方案优于其他文献报道的方案。结论：软X线对表皮恶性肿瘤是有效的。