Taurine entry into perilymph of the guinea pig

Taurine is a β-aminosulfonic acid and is a ubiquitous amino acid whose role in the cochlea is not well established. In this study, its entry from blood into perilymph was investigated in the guinea pig as animal model. The penetration rate of [³H]taurine (molecular weight 125) into the perilymph of the scala vestibuli was measured 1 and 2 h after the intravenous infusion of [³H]taurine in nephrectomized animals. Results showed a rate of penetration in perilymph related to plasma at 36 ± 4.7% (n = 5) after 1 h and 43 ± 5.6% (n = 5) after 2 h. Compared to the penetration rate of urea (molecular weight 60) and mannitol (molecular weight 186) reported previously in rats, a passive entry of taurine into perilymph through the blood-perilymph barrier is suggested. Received: 30 July 1997 / Accepted: 15 January 1998     

Liver transplantation, including the concept of reduced-size liver transplants in children.

Since the establishment of a clinical program in liver transplantation in 1984, 162 liver transplants have been performed in 131 patients (78 adults, 53 children). The patient mortality rate while waiting for a suitable organ has been 8% for adults and only 4% for children (25-46% reported in the literature). The low pediatric mortality is a result of the use of reduced-size liver transplants. A total of 14 procedures have been performed in recipients whose clinical condition was deteriorating and for whom no full-size graft could be located. Of 14 children, 13 were less than 3 years of age. Patient survival is 50%, comparable to survival of high-risk recipients of full-size livers. Using reduced-size liver grafting in a transplant program can lower mortality for children awaiting a transplant by overcoming size disparity. Reduced-size liver grafting will allow more effective use of donor resources and provide a potential avenue of research for organ splitting and living related donation.     

Contribution of BK Ca2+-activated K+ channels to auditory neurotransmission in the Guinea pig cochlea

Large-conductance calcium-activated potassium (BK) channels are known to play a prominent role in the hair cell function of lower vertebrates where these channels determine electrical tuning and regulation of neurotransmitter release. Very little is known, by contrast, about the role of BK channels in the mammalian cochlea. In the current study, we perfused specific toxins in the guinea pig cochlea to characterize the role of BK channels in cochlear neurotransmission. Intracochlear perfusion of charybdotoxin (ChTX) or iberiotoxin (IbTX) reversibly reduced the compound action potential (CAP) of the auditory nerve within minutes. The cochlear microphonics (CM at f1 = 8 kHz and f2 = 9.68 kHz) and their distortion product (DPCM at 2f1-f2) were essentially not affected, suggesting that the BK specific toxins do not alter the active cochlear amplification at the outer hair cells (OHCs). We also tested the effects of these toxins on the whole cell voltage-dependent membrane current of isolated guinea pig inner hair cells (IHCs). ChTX and IbTX reversibly reduced a fast outward current (activating above -40 mV, peaking at 0 mV with a mean activation time constant tau ranging between 0.5 and 1 ms). A similar block of a fast outward current was also observed with the extracellular application of barium ions, which we believe permeate through Ca2+ channels and block BK channels. In situ hybridization of Slo antisense riboprobes and immunocytochemistry demonstrated a strong expression of BK channels in IHCs and spiral ganglion and to a lesser extent in OHCs. Overall, our results clearly revealed the importance of BK channels in mammalian cochlear neurotransmission and demonstrated that at the presynaptic level, fast BK channels are a significant component of the repolarizing current of IHCs.     

Sex and Drug Risk Behavior Pre- and Post-Emigration Among Latino Migrant Men in Post-Hurricane Katrina New Orleans

High rates of sex and drug risk behaviors have been documented among Latino migrant men in the US. Whether these behaviors were established in the migrants’ home countries or were adopted in the US has not been described and has implications for prevention strategies. Quarterly surveys were conducted to gather information on selected sex and drug risk practices of Latino migrant men who arrived in New Orleans after Hurricane Katrina seeking work. Both kappa scores and McNemar’s tests were performed to determine if practice of these behaviors in home country was similar to practice post-emigration to the US. Female sex worker (FSW) patronage, same sex encounters (MSM), and crack cocaine use was more likely to occur post- rather than pre-emigration. Of those who ever engaged in these selected behaviors, most adopted the behavior in the US (i.e., 75.8 % of FSW patrons, 72.7 % of MSM participants, and 85.7 % of crack cocaine users), with the exception of binge drinking (26.8 %). Men who were living with a family member were less likely to adopt FSW patronage OR = 0.27, CI = 0.10–0.76, whereas men who earned >$465 per week were more likely to adopt crack cocaine use OR = 6.29 CI = 1.29, 30.57. Interventions that facilitate the maintenance of family cohesion and provide strategies for financial management may be useful for reducing sex and drug risk among newly arrived migrants.     

Fc-Fc interactions of human IgG4 require dissociation of heavy chains and are formed predominantly by the intra-chain hinge isomer

Human IgG4 antibodies are remarkable not only because they can dynamically exchange half-molecules (Fab-arm exchange) but also for their ability to interact with the Fc part of IgG4 and other IgG subclasses. This rheumatoid factor-like binding of IgG4 does not appear to take place spontaneously, because it is only observed to solid-phase or antigen-bound IgG. We hypothesized that Fc-Fc interactions might involve (partial) dissociation of heavy chains. We investigated the molecular basis of these Fc-Fc interactions, and found that the structural features important for the exchange reaction also control the Fc binding activity. In particular, if arginine-409 in the CH(3)-CH(3) interface in IgG4 is mutated to lysine (the equivalent in IgG1), Fc-Fc interactions are formed 3 orders of magnitude less efficiently compared to the wild-type. This mutation was previously found to increase the CH(3)-CH(3) interaction strength in IgG4. Furthermore, of the two hinge isomers of IgG4, the intra-chain (non-covalently linked) form was found to form Fc-Fc interactions, but not the inter-chain form. Together, these results demonstrate that Fc-Fc interactions of IgG4 involve (partial or complete) dissociation of heavy chains. The promiscuity to other IgG subclasses suggests that IgG4 might act as scavenger to IgG molecules with impaired structural integrity.     

An evaluation of clinical stability criteria to predict hospital course in community-acquired pneumonia

A number of different methods exist to assess clinical stability, a key component of pneumonia management. We compared the prognostic value of different stability criteria through a secondary analysis of the Edinburgh pneumonia study database. We studied four clinical stability criteria (Halm's criteria, the ATS criteria, CURB and 50% or more decrease in C-reactive protein from baseline). Outcomes included 30-day mortality, need for mechanical ventilation or vasopressor support (MV/VS), development of a complicated pneumonia, and a combined outcome of the above. A total of 1079 patients (49.8% male), with a median age of 68 years (IQR 53–80), were included. Ninety-three patients (8.6%) died by day 30, 91 patients (8.4%) required MV/VS and 99 patients (9.2%) developed a complicated pneumonia. Patients with increasing severity of pneumonia on admission, assessed by both CURB-65 and PSI, took a progressively longer time to achieve clinical stability assessed by any method (p < 0.001 for all criteria). Halm's criteria had the highest area under the curve (AUC) for prediction of 30-day mortality (AUC 0.95 (0.94–0.96)), need for MV/VS (AUC 0.96 (0.95–0.97)) and combined adverse outcome (AUC 0.96 (0.95–0.97)). C-reactive protein had the highest area under the curve for complicated pneumonia (AUC 0.96 (0.95–0.97)). Adding C-reactive protein to Halm's criteria increased the area under the curve, but the difference was only statistically significant for complicated pneumonia. All of the criteria performed well in predicting adverse outcomes in patients with pneumonia. Halm's criteria performed best when identifying patients at low risk of complications.     

Ulnar Nerve Innervation of the Triceps Muscle: Real or Apparent? An Anatomic Study

Background

Since the 18th century, the existence of ulnar nerve innervation of the medial head of the triceps brachii muscle has been controversial. The evidence for or against such innervation has been based on macroscopic dissection, an unsuitable method for studying intraneural topography or intramuscular branching. The study of smaller specimens (embryos or fetuses) by means of serial histologic sections may resolve the controversy.

Questions/Purposes

Using fetal specimens and histology we determined the contributions of the ulnar and radial nerves to innervation of the triceps brachii muscle.

Methods

We histologically examined 15 embryonic and fetal arms. Radial nerve branches obtained from six adult arms were analyzed immunohistochemically to determine motor fiber content.

Results

The medial head of the triceps brachii muscle was always innervated by the radial nerve (ulnar collateral branch). The branches seeming to leave the ulnar nerve at elbow level were the continuation of the radial nerve that had joined the ulnar nerve sheath via a connection in the axillary region. Immunohistochemistry revealed motor and nonmotor fibers in this radial nerve branch.

Conclusions

A connection between the radial and ulnar nerves sometimes may exist, resulting in an apparent ulnar nerve origin of muscular branches to the medial head of the triceps, even though in all our specimens the fibers could be traced back to the radial nerve.

Clinical Relevance

Before performing or suggesting new muscle and nerve transpositions using this apparent ulnar innervation, the real origin should be confirmed to avoid failure.