Sodium‐dependent vitamin C transporter‐2 mediates vitamin C transport at the cortical nerve terminal

It has been shown that vitamin C (VC) is transported at synaptic boutons, but how this occurs has not been elucidated. This study investigates the role of the sodium‐dependent vitamin C transporter‐2 (SVCT2) in transporting VC at the cortical nerve terminal. Immunostaining of cultured mouse superior cervical ganglion cells showed the SVCT2 to be expressed in presynaptic boutons, colocalizing with the vesicular monoamine transporter‐2 and the norepinephrine transporter. Immunoblotting of enriched cortical synaptosomes demonstrated that the SVCT2 was enriched in presynaptic fractions, confirming a predominantly presynaptic location. In crude synaptosomes, known inhibitors of SVCT2 inhibited uptake of VC. Furthermore, the kinetic features of VC uptake were consistent with SVCT2‐mediated function. VC was also found to efflux from synaptosomes by a mechanism not involving the SVCT2. Indeed, VC efflux was substantially offset by reuptake of VC on the SVCT2. The presence and function of the SVCT2 at the presynaptic nerve terminal suggest that it is the transporter responsible for recovery of VC released into the synaptic cleft. © 2015 Wiley Periodicals, Inc.     

Marrow harvesting from normal donors

The experience at a single institution in harvesting marrow for allogeneic transplantation on 1,270 occasions from 1,160 normal donors is presented in detail, together with an analysis of all the donor complications. Four donors were less than 2 years old, and the youngest was 6 1/2 months. No special difficulties were encountered with these young donors. Hospitalization time was three days or less for 99% of the procedures. Six donors had life-threatening complications; three of a cardiopulmonary and two of an infectious nature, and one cerebrovascular embolic episode. Significant operative site morbidity, usually transient neuropathies, occurred in ten procedures. Ten percent of the donations were associated with transient postoperative fever of unknown origin. Increasing donor age was associated with a reduction of the cellularity of the marrow harvest. The use of stored autologous blood permitted the avoidance of blood bank transfusion in 81% of males, 69% of females, and 50% of children. It was concluded that the procedure was associated with a very low risk of complication, but that the involvement of normal donors in such an operation justifies stringent monitoring.     

Analysis of the relationship between age and treatment response in migraine

In migraine, headache severity varies with age. As a consequence, the effectiveness of medication may also depend on a patient's age. The purpose of this study was to assess the combined effect of age and drug treatment on headache characteristics. Using data from clinical trials of sumatriptan in adolescents and adults, we show how the interaction between age and drug exposure can be parameterised as a covariate on a Markov model that describes the decline of headache severity over three clinically defined stages (no relief, relief and pain-free status). The model explains important clinical observations: (i) the rates at which the pain relief and pain-free status were attained were found to be inversely related to age; (ii) in placebo-treated patients, the mean transit time from 'no relief' to 'relief' is 3 h for young adolescents and increases to 6 h for patients aged ≥ 30 years; and (iii) sumatriptan reduces the transit time to 2 h, irrespective of age. These findings indicate that the therapeutic gain over placebo increases with age. Prospective studies of antimigraine drugs should take this relationship into account when extrapolating efficacy data from adults to adolescents.     

Facial motor evoked potentials in cerebellopontine angle surgery: technique, pitfalls and predictive value

Objective

To obtain information on functional integrity of the facial nerve by transcranial electrical motor evoked potentials independent of nerve visualization and to improve prediction of postoperative function.

Patients and methods

In a prospective clinical study, 68 patients with cerebello-pontine angle tumors and 5 patients with trigeminal neuralgia were investigated by facial motor evoked potentials (FMEP) elicited by multi-pulse transcranial electrical motor cortex stimulation. For recording the same electrode set-up was used as for continuous EMG monitoring of the orbicularis oculi and oris muscles. Pre-surgical FMEP amplitudes and latencies were correlated with tumor extensions. End to start amplitude ratios were compared to early and long-term facial nerve function by House-Brackmann-Grading (HB) documented by pre- and post-operative photo and video documentation.

Results

Reliable FMEP were obtained in 57 patients. FMEP responses at the start of surgery correlated with the degree of tumor extension. Largest FMEP amplitudes and shortest latencies were found in patients with trigeminal neuralgia. FMEP quality was reduced with increasing tumor extension (P < 0.05). The ratio of end-operative to start-operative FMEP-amplitude showed a positive correlation with early and late facial nerve function. Correlation was especially close with early function: an amplitude preservation rate of 86% led to HB°1 or HB°2, of 67% to HB°3, at 33% to HB°4 and at 15% or lower to HB°5 or HB°6.

Discussion

Initial FMEP amplitudes correlate with the presumed pre-operative nerve affection by space occupying tumors, a phenomenon reported here for the first time. Intact FMEP are highly reliable for preserved nerve continuity and hereby are of special help to the neurosurgeon for those surgical phases where the facial nerve is not visible and still covered by tumor and where conventional EMG monitoring is of very limited use. The end-to-start amplitude ratio of the FMEP is closely related to early and late clinical function. Amplitude reduction by 30% or more should result in a change of microsurgical action to enable fast recovery.

Conclusion

As an adjunct to intraoperative EMG, FMEP are superior in two respects, first in identifying pre-surgical latent nerve lesions and second in monitoring nerve integrity without direct nerve visualization. FMEP are highly reliable in predicting early and late postoperative function.     

Marrow transplantation with or without donor buffy coat cells for 65 transfused aplastic anemia patients

Sixty-five multiply transfused patients with severe aplastic anemia were given cyclophosphamide followed by grafts anemia were given cyclophosphamide followed by grafts from HLA-identical siblings. The effect of the administration of viable donor buffy coat cells following the marrow inoculum was evaluated with regard to graft rejection and survival. Results in 43 patients so treated are presented along with those in 22 concurrent patients given marrow alone. Most patients given buffy coat had positive in vitro tests of sensitization indicating a high risk for graft rejection, while all but one of the patients given marrow alone had negative tests. Thirty of the 43 (70%) patients given marrow and buffy coat are alive between 10 and 61 mo (median 36) after grafting; 4 died after graft rejection and 6 with acute or chronic graft-versus-host disease (GVHD). Eleven of the 22 (50%) patients given marrow alone are alive between 29 and 65 mo (median 52); 7 died after graft rejection and 3 with GVHD. The addition of buffy coat cell infusions to the marrow inoculum reduced the risk of rejection and increased survival in the currently reported transfused patients when compared to patients grafted before 1976. However, there was an increased risk of chronic GVHD. Recipients of marrow from female donors survived slightly better (73%) than recipients of male marrow (58%).     

Symptoms of ＂Heat＂ as a Pattern of Physiopathology

Objective： The guiding criteria are considered the backbone of Chinese medicine. They have previously been described as functional features （symptoms） leading to the overall assessment of human functions on the basis of a regulatory （cybernetic） model referring to the I Ging. Methods： The Heidelberg model can explain symptoms such as created by ＂heat＂ on a rational physiological level. Results ＆ Conclusion： The overall of physiological symptoms are shown as a schematic draft. The basis of ＂heat＂ is considered to be a general increase of microcirculation in the periphery. This leads to a couple of local pathophysiological consequences and sensations like 1） red tongue （the tongue is considered an embryological somatotopic system）. 2） Sensation of warmth （by increase of capillary flow）. 3） pre-inflammatory state, leading to pain modalities like ＂worse if pressed＂, as inflammations tend to be increasingly painful under pressure; 4） reddish skin, the mechanisms by which this is induced may include the release of substance P, therefore accompanied by burning sensation. Systemic pathophysiological consequences may include. Relative lack of fluid in the larger vessels, as fluid supplies peripheral capillary flow. This may lead to water saving mechanisms like thirst, dry mucosa with do, mouth, dry nose, dry lips, dry skin, and also dry stool, yellow and sparse urine.     

Mammography in women less than 40 years of age

Carcinoma of the breast in women less than 40 years old is a significant problem, representing 7.4 per cent of the total number of carcinomas of the breast at our institution. It is apparent that mammography in this age group is of value in confirming the clinical suspicion of a malignant condition of the breast and in evaluating the remainder of the parenchyma of the breast for clinically occult lesions. However, one cannot over emphasize that a negative result from the mammogram should not delay biopsy in the presence of clinically suspicious lesions (1, 4). It is obvious that a larger series of patients is necessary to define the role of mammography in "young women."     

Vestibular schwannomas and auditory function: options in large T3 and T4 tumors?

OBJECTIVE: While hearing preservation has become an accepted treatment goal, there are still major doubts whether and to what extent this aim is feasible in large tumors that cover the auditory nerve and involve the brainstem. METHODS: One thousand eight hundred (1,800) vestibular schwannomas (VS) were operated on at Nordstadt Neurosurgical Department from 1978 to 1999 by the senior surgeon (MS). There were 1,800 tumors in 1,750 patients, 1,605 patients had unilateral tumors, 145 patients had neurofibromatosis type 2 with bilateral tumors, 195 of which were treated surgically in our unit. Preservation of the cochlear nerve was attempted when ever possible. The audiometric data are analyzed by Hannover Classification System graded in steps of 20 dB by audiometry and in steps of 10% to 30% by speech discrimination. Those data were set into relation with the Hannover tumor extension grading T1 to T4. RESULTS: Overall preservation rate was 40% with considerable differences, though, depending on the preoperative hearing quality and the tumor extension. Best results were obtained for intrameatal tumors (T1) with 56% and small intra-extrameatal tumors (T2) with 57% preservation rate. While preservation rate was at 44% in medium-sized tumors (T3), it was at 20% for T4 tumors with brainstem compression or even dislocation. However, satisfactory chances were encountered in cases with normal or good preoperative hearing, on average 54%, specifically 71% in T1, 69% in T2, 58% in T3 and 29% in T4. Regarding the quality of the preserved hearing, up to one third of cases in T1 and T2 may retain their preoperative hearing level, while this ranges around 20% for T3 and 10% to 14% in T4 tumors. DISCUSSION: For long, hearing preservation in medium sized or large tumors has not received any attention because of the presumed lack of realistic chances and the expected bad quality. Obviously, hearing preservation may be achieved in relevant numbers and at satisfactory quality levels. This aspects appears important to be addressed further in view of the fact that over 70% of tumors are presented for surgery at T3 or T4 extensions. CONCLUSION: The summit of hearing preservation has not been reached as improvements are still achieved even in most difficult conditions.