Human cytomegalovirus seropositivity is associated with reduced patient survival during sepsis.

BACKGROUND: Sepsis is one of the leading causes of death. Treatment attempts targeting the immune response regularly fail in clinical trials. As HCMV latency can modulate the immune response and changes the immune cell composition, we hypothesized that HCMV serostatus affects mortality in sepsis patients. METHODS: We determined the HCMV serostatus (i.e., latency) of 410 prospectively enrolled patients of the multicenter SepsisDataNet.NRW study. Patients were recruited according to the SEPSIS-3 criteria and clinical data were recorded in an observational approach. We quantified 13 cytokines at Days 1, 4, and 8 after enrollment. Proteomics data were analyzed from the plasma samples of 171 patients. RESULTS: The 30-day mortality was higher in HCMV-seropositive patients than in seronegative sepsis patients (38% vs. 25%, respectively; p = 0.008; HR, 1.656; 95% CI 1.135-2.417). This effect was observed independent of age (p = 0.010; HR, 1.673; 95% CI 1.131-2.477). The predictive value on the outcome of the increased concentrations of IL-6 was present only in the seropositive cohort (30-day mortality, 63% vs. 24%; HR 3.250; 95% CI 2.075-5.090; p < 0.001) with no significant differences in serum concentrations of IL-6 between the two groups. Procalcitonin and IL-10 exhibited the same behavior and were predictive of the outcome only in HCMV-seropositive patients. CONCLUSION: We suggest that the predictive value of inflammation-associated biomarkers should be re-evaluated with regard to the HCMV serostatus. Targeting HCMV latency might open a new approach to selecting suitable patients for individualized treatment in sepsis.

[Osteosynthetic treatment of proximal femoral fractures: the timing of treatment is delayed in cases of pre-existing anticoagulation : Results of the data of external inpatient quality assurance from North Rhine-Westphalia with 24,786 cases within the framework of using secondary data]. / Proximale osteosynthetisch versorgte Femurfrakturen: Der Versorgungszeitpunkt verzögert sich bei vorbestehender Antikoagulation : Ergebnisse der Daten der externen stationären Qualitätssicherung aus Nordrhein-Westfalen mit einer Fallzahl von 24.786 Fällen im Rahmen sekundärer Datennutzung.

BACKGROUND AND OBJECTIVE: Proximal femoral fractures are common in Germany with approximately 100,000 affected patients per year. The mortality could be considerably reduced by timely treatment (<24 h). The objectives of this work were to demonstrate the prevalence of anticoagulation and associated complications in osteosynthetically treated proximal femoral fractures, the impact of anticoagulation on the preoperative period and potential optimization of perioperative anticoagulation management. MATERIAL AND METHODS: External quality control data for North Rhine-Westphalia for the years 2015-2016 were evaluated. Only cases in which a femoral fracture near the hip joint was treated osteosynthetically were analyzed. A total of 24,786 cases of femoral fractures near the hip joint were included in the study. RESULTS: In the largest subgroup with acetylsalicylic acid (ASS) medication (n = 4005) 17% underwent delayed surgery, in the second largest group with vitamin K antagonists (VKA, n = 2157) 44.6% underwent delayed surgery and in the third largest group with direct oral anticoagulant (DOACs) medication (n = 994) 18.2% underwent delayed surgery. CONCLUSION: The biggest potential of shortening the preoperative period can be found in the ASS and vitamin K antagonist subgroups (17% and 44.6% delayed surgery, respectively). The antagonization of the effect of VKA can be achieved within a short time by the administration of prothrombin complex (PPSB). Even when taking DOACs, the current common procedure of delayed surgical treatment must be critically questioned. A coagulation management should be established in the SOP. In addition to medical interventions (administration of antidotes), structures must be created that enable prompt care.

Two candidate genes (FTO and INSIG2) for fat accumulation in four canids: chromosome mapping, gene polymorphisms and association studies of body and skin weight of red foxes.

Fat accumulation is a polygenic trait which has a significant impact on human health and animal production. Obesity is also an increasingly serious problem in dog breeding. The FTO and INSIG2 are considered as candidate genes associated with predisposition for human obesity. In this report we present a comparative genomic analysis of these 2 genes in 4 species belonging to the family Canidae - the dog and 3 species which are kept in captivity for fur production, i.e. red fox, arctic fox and Chinese raccoon dog. We cytogenetically mapped these 2 loci by FISH and compared the entire coding sequence of INSIG2 and a fragment of the coding sequence of FTO. The FTO gene was assigned to the following chromosomes: CFA2q25 (dog), VVU2q21 (red fox), ALA8q25 (arctic fox) and NPP10q24-25 (Chinese raccoon dog), while the INSIG2 was mapped to CFA19q17, VVU5p14, ALA24q15 and NPP9q22, respectively. Altogether, 29 SNPs were identified (16 in INSIG2 and 13 in FTO) and among them 2 were missense substitutions in the dog (23C/T, Thr>Met in the FTO gene and 40C/A, Arg>Ser in INSIG2). The distribution of these 2 SNPs was studied in 14 dog breeds. Two synonymous SNPs, one in the FTO gene (-28T>C in the 5'-flanking region) and one in the INSIG2 (10175C>T in intron 2), were used for the association studies in red foxes (n = 390) and suggestive evidence was observed for their association with body weight (FTO, p < 0.08) and weight of raw skin (INSIG2, p < 0.05). These associations indicate that both genes are potential candidates for growth or adipose tissue accumulation in canids. We also suggest that the 2 missense substitutions found in dogs should be studied in terms of genetic predisposition to obesity.

Use of palivizumab in Germany: data from 2002-2007.

BACKGROUND: The German Palivizumab Registry refers to a post-marketing observational study of palivizumab administration during 5 consecutive respiratory syncytial virus (RSV) seasons (2002/2003 -2006/2007). PATIENTS AND METHODS: The registry provided data on drug administration, risk factors for complicated RSV disease, rehospitalisation rates for infants receiving RSV prophylaxis, and parental adherence. 49608 administrations were documented in 10686 patients (average of 4.6 per patient). RESULTS: 35% of infants received >5 monthly injections. Median gestational age at birth was 29 weeks (range 23-41 weeks), median birth weight was 1350 g (range 320-6620 g), 3% were attending day care, 46% lived in a household with children <12 years, 18% were exposed to tobacco smoke at home, 10% had a family history of asthma, and 31% had congenital heart disease. The risk of serious adverse events possibly or probably related to palivizumab administration was 0.2 per 1000 administrations. According to a worst-case calculation, the rehospitalisation rate related to RSV infection was 2.5% in children who received prophylaxis. CONCLUSION: The German Palivizumab Registry provides a comprehensive dataset describing the use of palivizumab in Germany from 2002 to 2007, and areas for improvement identified in this registry can be applied to enhance the use of palivizumab in the future.

A pharmacometric approach to define target site-specific breakpoints for bacterial killing and resistance suppression integrating microdialysis, time-kill curves and heteroresistance data: a case study with moxifloxacin.

OBJECTIVES: Pharmacokinetic-pharmacodynamic (PK-PD) considerations are at the heart of defining susceptibility breakpoints for antibiotic therapy. However, current approaches follow a fragmented workflow. The aim of this study was to develop an integrative pharmacometric approach to define MIC-based breakpoints for killing and suppression of resistance development for plasma and tissue sites, integrating clinical microdialysis data as well as in vitro time-kill curves and heteroresistance information, exemplified by moxifloxacin against Staphylococcus aureus and Escherichia coli. METHODS: Plasma and target site samples were collected from ten patients receiving 400 mg moxifloxacin/day. In vitro time-kill studies with three S. aureus and two E. coli strains were performed and resistant subpopulations were quantified. Using these data, a hybrid physiologically based (PB) PK model and a PK-PD model were developed, and utilized to predict site-specific breakpoints. RESULTS: For both bacterial species, the predicted MIC breakpoint for stasis at 400 mg/day was 0.25 mg/L. Less reliable killing was predicted for E. coli in subcutaneous tissues where the breakpoint was 0.125 mg/L. The breakpoint for resistance suppression was 0.06 mg/L. Notably, amplification of resistant subpopulations was highest at the clinical breakpoint of 0.25 mg/L. High-dose moxifloxacin (800 mg/day) increased all breakpoints by one MIC tier. CONCLUSIONS: An efficient pharmacometric approach to define susceptibility breakpoints was developed; this has the potential to streamline the process of breakpoint determination. Thereby, the approach provided additional insight into target site PK-PD and resistance development for moxifloxacin. Application of the approach to further drugs is warranted.

[Venous aneurysmatic malformation of the chest wall as a rare cause of pulmonary embolism--a case report]. / Kalzifizierende venös-aneurysmatische Malformation der Thoraxwand als seltene Ursache von Lungenembolien--eine Kasuistik.

This is a case report about a 66-year old man with recurrent pulmonary embolisms. Phlebography revealed a monstrous venous aneurysm of the right chest wall with several venous dilatations and calcification as the source of the embolism. Radiological embolisation and surgical ligation of the large aneurysmatic neck were performed. No further embolism episodes were registered under anticoagulation during the 23 months of the postoperative follow-up investigation.

Hypomagnesemia in type II diabetes: effect of a 3-month replacement therapy.

OBJECTIVE: To investigate the effects of long-term high-dose oral magnesium (Mg) therapy (30 mmol/day) in patients with type II diabetes. Low plasma magnesium levels have been reported in type II diabetes and are associated with insulin resistance and diabetic late complications. RESEARCH DESIGN AND METHODS: Forty patients with type II diabetes and hypomagnesemia were observed in a randomized double-blind placebo-controlled trial for 3 months (body mass index: 28 +/- 4 kg/m2; HbA1c: 7.4 +/- 0.8%). Plasma and urine magnesium and metabolic control parameters were determined, and side effects were considered, especially with regard to patients' compliance. RESULTS: A significant increase in plasma magnesium levels was observed after 3 months of treatment (Mg: 0.73 +/- 0.8 vs. 0.81 +/- 0.1 mmol/l), reaching magnesium levels of the control group (0.88 +/- 0.8 mmol/l; NS); metabolic control, however, was not altered (HbA1c: 7.2 +/- 0.7 vs. 7.4 +/- 0.9%). Six months after the end of the trial, plasma magnesium declined to pretreatment levels (Mg: 0.73 +/- 0.07 mmol/l). The prevalence of side effects was high at the beginning and was reduced significantly during treatment. CONCLUSIONS: We conclude that oral magnesium replacement therapy corrects hypomagnesemia after a minimum treatment period of 3 months. These observations might be important for the prevention of diabetic late complications.

Abnormalities of auditory evoked magnetic fields and structural changes in the left hemisphere of male schizophrenics--a magnetoencephalographic-magnetic resonance imaging study.

Functional and structural changes in 10 DSM-III-R male schizophrenics and 10 healthy volunteers were investigated using magnetoencephalographically (MEG) detected long-latency (N100 m) auditory evoked fields (AEFs) and magnetic resonance imaging (MRI). The AEFs were characterized by single moving equivalent dipoles, which were superimposed on MRIs. There were significant differences in dipole orientations and in AEF latencies in the left hemisphere of schizophrenics, when compared to the controls. The MEG-detected alterations were found to be associated with a bilateral volume reduction of the posterior superior temporal gyrus (pSTG), which was more pronounced in the left hemisphere. Separate analysis of white and gray matter has shown that the pSTG volume reduction resulted from decreased gray matter volumes without white matter changes. Both the functional and the morphological data indicate a left-hemispheric disturbance in our patients.

Cloning and characterization of the rat 5-HT5B receptor. Evidence that the 5-HT5B receptor couples to a G protein in mammalian cell membranes.

A gene encoding a novel G protein-coupled 5-hydroxytryptamine (5-HT) receptor, termed 5-HT5B, was cloned. The ligand binding profile of this receptor is distinct from that of other cloned 5-HT receptors. The 5-HT5B receptor couples to a G protein in COS1 cell membranes; however, activation of the 5-HT5B receptor does not appear to alter either cAMP accumulation or phosphoinositide turnover in a variety of fibroblast cell lines. In the rat brain, 5-HT5B gene expression occurs predominantly in the medial habenulae and hippocampal CA1 cells of the adult. Little expression is seen during embryonic development.

Pharmacological profile of tazasubrate, a new cholesterol-lowering agent.

The properties of tazasubrate (2-phenyl-2-[(6-ethoxy-2-benzothiazolyl)thio]propionic acid), a potent hypocholesterolemic agent, were studied in rats. Tazasubrate was found to be a reliable and highly effective hypocholesterolemic agent. There was a marked and reproducible reduction of serum cholesterol in various rat models differing in age, sex and diet, an improvement of the pathological lipoprotein pattern, slight but variable effects on serum triglycerides and phospholipids, no accumulation of intermediates of cholesterol biosynthesis, no inhibition of phospholipid metabolism (i.e. no induction of phospholipidosis), no interaction with the thyroid gland, and in contrast to fibrates, only minimal induction of peroxisomes in hepatocytes.

A new medical approach to the treatment of osteoarthritis. Report of an open phase IV study with ademetionine (Gumbaral).

A non-controlled clinical phase IV trial was carried out involving 20,641 patients with osteoarthritis of the knee, the hip, and the spine and also with osteoarthritic polyarthritis of the fingers, who were treated with ademetionine tablets given in a fixed dosage schedule for eight weeks. No additional analgesic/antirheumatic treatment was allowed. Nevertheless, concomitant medication for other diseases was permissible. The efficacy was described as "very good" or "good" in 71 percent of cases, as "moderate" in 21 percent, and as "poor" in 9 percent of cases. The tolerance was assessed as very good or good in 87 percent, as moderate in 8 percent, and as poor in 5 percent of cases. The trial therapy was discontinued prematurely because of symptoms of intolerance in 5 percent of the patients and because of a lack of efficacy in 2.3 percent of cases.

Postoperative local radiotherapy in rectal cancer: treatment results with limited radiation fields.

PURPOSE: The purpose of this study is to determine the treatment results and complication rates of postoperative local radiotherapy, with doses per fraction of 2.25 to 2.50 Gy, in patients with rectal carcinoma who have received macroscopically radical surgery. METHODS AND MATERIALS: A retrospective analysis was done of the records of all consecutive patients (N = 147) with rectal carcinoma Dukes' Stage B or C who have received postoperative local radiotherapy in our institution in the years 1981 through 1989. All patients have been treated on a limited target area covered by only local radiation fields. Locoregional fields covering the whole iliac node chains have not been given. In our treatment protocol doses per fraction were from 2.25 to 2.50 Gy and total doses from 50 to 55 Gy. The minimum follow-up was 24 months; eight patients have been lost to follow-up. RESULTS: The overall 5-year survival rate for the whole group of patients was 39%. The actuarial 2- and 5-year pelvic recurrence rates were 14% and 22% respectively for Dukes' B patients and 30% and 38% respectively for Dukes' C patients. The difference between the pelvic recurrence rates of Stage B and Stage C patients was statistically significant (p = 0.009). No other factors with prognostic significance for pelvic recurrence were found. The interval between surgery and radiotherapy especially had no influence on pelvic recurrence rates. The 35 pelvic recurrences were classified as follows: 17 in-field, 5 marginal, 1 out-of-field, and 9 peritoneal seeding; in three patients there was not enough information for classification. Of the 32 classified pelvic recurrences, the five marginal recurrences were probably geographical misses, only the one out-of-field recurrences, the five marginal recurrences were probably geographical misses; only the one out-of-field recurrence might have been prevented with locoregional radiotherapy. Serious complications caused by the radiotherapy have occurred in 3% of the patients. CONCLUSION: We conclude that the results of postoperative local radiotherapy alone are comparable with the published results of locoregional radiation. Even when relatively high doses per fraction are given low complication rates are seen.

[3H]-5-carboxamidotryptamine labels 5-HT1D binding sites in bovine substantia nigra.

1. [3H]-5-hydroxytryptamine (5-HT) has been shown to radiolabel at least five types of 5-HT binding sites in mammalian brain tissue, 5-HT1A, 5-HT1C, 5-HT1D and 5-HT1D and 5-HT1E (Frazer et al., 1990). Selective masking of 5-HT1A and 5-HT1C receptors, has uncovered binding sites which display both high (5-HT1D) and low (5-HT1E) affinity for 5-carboxamidotryptamine (5-CT). By utilizing [3H]-5-CT we have eliminated a portion of the complex binding (5-HT1E) seen when [3H]-5-HT is used as a radioligand. 2. [3H]-5-CT binding to 5-HT1D sites in bovine substantia nigra was rapid, reversible and saturable, displaying high affinity (Kd = 0.38 +/- 0.04 nM) and low non-specific binding (> 90% specific binding). 3. In bovine substantia nigra, [3H]-5-CT labelled an equivalent number of binding sites to [3H]-5-CT (403 +/- 18 and 362 +/- 20 fmol mg-1 protein, respectively) and binding was sensitive to guanine nucleotides. 4. A linear correlation (r2 = 0.99) existed between the potency of compounds to displace [3H]-5-HT and [3H]-5-CT in bovine substantia nigra. 5. Therefore, [3H]-5-CT is a novel radioligand for the examination of 5-HT1-like binding sites, which under proper experimental conditions can be used to radiolabel selectively 5-HT-1D-like binding sites.

Cloning and characterization of the rat GALR1 galanin receptor from Rin14B insulinoma cells.

Galanin is a ubiquitous neuropeptide that regulates a wide array of physiological processes via interaction with specific G protein-coupled receptors. A rat galanin receptor cDNA was cloned from the Rin14B insulinoma cell line. The isolated cDNA encodes a 346 amino acid G protein-coupled receptor that is 92% identical to the recently reported human GALR1 galanin receptor. [125I]Galanin binds with high affinity to two receptor states in COS1 cell membranes containing the rat GALR1 receptor, consistent with coupling of the receptor to a G protein in these membranes. N-terminal galanin fragments and the putative galanin receptor antagonists galantide, C7, M35 and M40 bind with high affinity to the rat GALR1 receptor. In contrast, C-terminal galanin fragments do not bind to this receptor. Galanin inhibits basal and forskolin-stimulated cAMP formation in CHO cells expressing the rat GALR1 receptor via a pertussis toxin-sensitive G protein. The GALR1 receptor is expressed in rat spinal cord, small intestine, Rin14B insulinoma cells and several brain regions, particularly ventral hippocampus, amygdala, supraoptic nucleus, hypothalamus, thalamus, lateral parabrachial nucleus and locus coeruleus. Cloning of the rat GALR1 galanin receptor cDNA will permit many new experimental strategies to be applied to studies of the structure and function of galanin receptors.

Neuronavigation in surgery of intracranial and spinal tumors.

PURPOSE: To demonstrate the new possibilities and advantages of neuronavigation in the surgery of intracranial and spinal tumors, based on patient populations treated in our hospital. MATERIALS AND METHODS: An infrared navigation system with integrated microscope guidance was used for frameless intracranial neuronavigation. The biopsies of intracranial tumors were carried out using a frame-based stereotactic technique. Intracranial navigation was, in part, combined with the use of an intraoperative CT scanner and a three-dimensional ultrasound system for data acquisition, correction of brain shifts, and intraoperative quality control. The navigation was also supported by presurgical brain mapping with magnetic source imaging. Navigation in spinal surgery was exclusively performed using an infrared navigation system in combination with an intraoperative CT scanner. RESULTS: The stereotactic tumor biopsies (n = 57) were carried out with an accuracy of 91.4% as compared with the histological diagnosis. The work flow of stereotactic procedures could be increased by using the intraoperative CT scanner. Fifty-seven patients with intracranial tumors were treated with the aid of neuronavigation between July 1997 and December 1999. These patients showed an improvement from 80% to 86% on the Karnofsky index 8 weeks postoperatively. The majority of intracranial cases were primary brain tumors (n = 30) and metastases (n = 13) in functionally important areas of the brain. In four patients, a significant brain shift was observed during neuronavigation, and could be corrected by an image update using either the intraoperative CT scanner (n = 2) or the three-dimensional ultrasound system (n = 2). The presurgical brain mapping with magnetoencephalography was shown to be reliable in the sensory cortex (n = 25). Eleven patients with a thoracic or lumbar tumor were treated by open surgery or stabilization, using a combination of spinal neuronavigation and the intraoperative CT scanner. Two patients with spinal tumors underwent navigated biopsies. Neither of them showed a reduction in the clinical stage, but the Karnofsky index improved from 63% up to 72% 8 weeks postoperatively. CONCLUSION: Neuronavigation allows very precise intracranial and spinal surgery. The problem of brain shift during the navigation procedures has been solved by intraoperative image acquisition. The use of neuronavigation was shown to improve the postoperative quality of life of patients suffering from brain and spinal tumors.

Type II alveolar epithelial cells and free alveolar cells after intratumor TNF-alpha administration.

The experiment used Morris hepatoma 5123 series growing in muscles of the Buffalo rats. A suspension of 3 x 10(6) neoplastic cells was injected into the right hind leg of the animals. After fourteen days, TNF-alpha was administered into the tumour in a dose of 1.5 x 10(4) U/24 hours in 0.5 ml PBS solution. The group I animals were injected for 4 days and group II for 8 days. Control groups consisted of rats with injected Morris hepatoma which were given PBS solution instead of TNF-alpha (group III A and B) and animals without the hepatoma, given 4 or 8 TNF-alpha, respectively (groups IV A and B). In the present study, we have explored the effect of intratumor TNF-alpha administration on the composition of cells isolated from the lungs through multiple bronchoalveolar lavages (BAL). Ultrastructural evaluation of the pulmonary tissue was done using a transmission electron microscope (TEM), with special attention paid to type II alveolar epithelial cells and free alveolar cells. Examinations in TEM in groups I, II and IV (A and B) found, in the lumen of alveoli, an increase in the number of alveolar macrophages (AM) with morphological features of intensified activity and AM with numerous secondary lysosomes containing material of phospholipid structure. Also, numerous type II alveolar epithelial cells with emptied lamellar bodies were observed. The above mentioned changes were especially marked after eightfold TNF-alpha administration. In groups I, II and IV (A and B), compared with group III, a significant increase was found in the total number of cells isolated by BAL as well as in the number of cells with positive reaction in staining according to Beckstead's method. It may indicate that the changes in the parameters mentioned above are related to TNF-alpha action. The results obtained indicate the possibility of systemic effect of TNF-alpha after its administration into the experimental Morris hepatoma.

Abnormalities of auditory evoked magnetic fields in the right hemisphere of schizophrenic females.

Eight DSM-III-R female schizophrenics were investigated by magneto-encephalographically (MEG) detected long latency (N100m) auditory evoked fields (AEFs). In contrast to controls, in schizophrenics a lack of interhemispheric asymmetry was present, which was found to be due to alterations of the right hemisphere.

Impaired sensory processing in male patients with schizophrenia: a magnetoencephalographic study of auditory mismatch detection.

The generation of mismatch negativity (MMN) as a component of auditory evoked event-related brain potentials has been reported previously to be severely disturbed in patients with schizophrenia. In the present study, we extended these findings to magnetoencephalography and investigated the neuromagnetic mismatch field (MMNm) in 15 male schizophrenic inpatients as compared to 16 healthy male volunteers. A standard tone of 1000 Hz and three different types of mismatch (1050-Hz tone, 5000-Hz tone, tone omission) were employed within the same paradigm, each mismatch occurring with a 10% pseudorandom probability. After correction for eye artifacts, the mean global field power of the mismatch reaction was calculated. Mismatch generation in patients with schizophrenia proved to be significantly impaired for all three conditions. This result confirms the theory of impaired auditory information processing in patients with schizophrenia at the level of the primary auditory cortex. Deficient generation of MMNm probably represents an impaired generation and/or faster decay of the sensory memory trace on the basis of disturbed sensory processing in male patients with schizophrenia.

Effect of ketamine on the neuromagnetic mismatch field in healthy humans.

Mismatch negativity (MMN) is a component of the auditory evoked event-related potentials (ERP) that assesses automatic sound change detection and is disturbed in schizophrenic patients. Animal experimental evidence has linked the generation of MMN to the N-methyl-D-aspartate (NMDA) receptor. We investigated the neuromagnetic mismatch field (MMF) in healthy volunteers before and after intravenous application of a subanesthetic dose of the NMDA receptor antagonist ketamine (0.3 mg/kg). Ketamine had a significant influence on latency and dipole moment of the MMF, whereas the N100m latency of the standard tone was not prolonged and its dipole moment remained stable. Our results suggest that ketamine interferes with aspects of preattentive information processing and is in line with the view that disturbed NMDA receptor function may mediate the deficient auditory mismatch response in patients with schizophrenia.

Reorganization of the somatosensory cortex after amputation of the index finger.

Cortical reorganization occurs within the primary somatosensory and the primary motor cortex after amputation of the arm or forearm. Here we report on a patient showing cortical reorganization after amputation of his right index finger. Our findings indicate that the neural networks within the area of the amputated finger in the somatosensory cortex (SI) were invaded by neighbouring structures, i.e. of neural cell assemblies that subserve the thumb and middle finger of his right hand.