Epidural pethidine and bupivacaine in labour

A double-blind randomised study was performed to assess the value of the addition of pethidine 50 mg to the initial dose of bupivacaine given for epidural analgesia in labour. Forty-nine patients received either 1 ml of saline (n = 24), or 50 mg of pethidine (n = 25), added to 9 ml of 0.25% bupivacaine as an initial injection for intrapartum epidural analgesia. There was a significant increase in the mean duration of analgesia in the pethidine group. However, pethidine did not increase the speed of onset of analgesia, or improve the quality of analgesia.     

Chimaeric monoclonal antibodies encoded by the human VH26 gene from naïve transgenic mice display a wide range of antigen-binding specificities.

To elucidate the molecular basis for the ability of antibodies encoded by the human VH26 heavy-chain variable region gene to react with diverse antigens, we have generated 34 hybridomas secreting chimaeric monoclonal antibodies (human mu heavy chain/mouse light chains) from transgenic mice. The transgenic mice carry an immunoglobulin minilocus containing the human VH26 gene, human DH and JH gene segments, and genes encoding the human C mu region. The minilocus in these animals undergoes functional rearrangement resulting in the production of chimaeric antibodies in which human mu heavy chains utilizing the VH26 gene are paired with mouse kappa or lambda light chains. The hybridomas described in this study were generated from naïve animals and were selected solely on the basis of human mu-chain expression. The antibodies described have covalently attached mouse light chains and are multimeric in structure. The binding properties of the antibodies were examined using a panel of both self- and foreign antigens using enzyme-linked immunosorbent assays, agglutination or radio-immunoprecipitation assays and immunofluorescence. Chimaeric immunoglobulins from 21 of the 34 hybridoma clones (61.7%) reacted with one or more antigens, of which 13 (38.2%) reacted with more than two antigens. These studies demonstrate that the VH26 gene, in combination with human DH and JH gene segments, and mouse light-chain genes, is able to encode antibodies with a wide range of ligand-binding specificities. These findings have important implications in the context of the possible origins of autoantibodies encoded by VH26 which may play a role in the pathogenesis of a number of autoimmune conditions.     

Rearrangement of the human heavy chain variable region gene V3-23 in transgenic mice generates antibodies reactive with a range of antigens on the basis of VHCDR3 and residues intrinsic to the heavy chain variable region

To formulate a 'logic' for how a single immunoglobulin variable region gene generates antibodies with different antigen specificity and polyreactivity, we analysed chimeric antibodies produced in transgenic mice carrying the germ-line human V3-23 gene, multiple diversity (D) and joining (J) gene segments. Hybridomas producing antibodies encoded by the V3-23 gene in combination with different mouse Vkappa genes were obtained by fusion of splenocytes from transgenic mice. All antibodies had human mu-chains and mouse light chains, were multimeric in structure and expressed the human V3-23 gene. Nucleotide sequence analyses of genes encoding the heavy and light chains of 12 antibodies in relation to antigen specificity highlighted the importance of heavy chain variable region CDR3 in determining reactivity with different antigens. However, the results also suggest that non-CDR3 sequences intrinsic to the V3-23 gene itself may be involved in, or determine, the binding of the chimeric antibodies to some of the antigens tested in the current study.     

Impact of Perioperative Pain Control on Knee Range of Motion and Development of Arthrofibrosis Following Primary Total Knee Arthroplasty

BackgroundInadequate pain control following total knee arthroplasty (TKA) has been postulated to negatively impact knee range of motion (ROM). We sought to determine the association between perioperative pain levels and knee ROM at 3-month follow-up or need for manipulation under anesthesia (MUA).MethodsWe retrospectively reviewed 2243 primary TKAs performed from 2002 to 2019 at a single academic center using an institutional total joint registry. Mean age was 68, mean body mass index was 32.8, and 59% were female. Knee ROM was measured preoperatively and 3 months postoperatively. Change in knee ROM, rates of soft tissue contracture, and MUA were assessed in relation to in-hospital 10-point pain visual analog scale (VAS) measurements.ResultsOverall, 44% had improved ROM at 3-month follow-up, 29% had no change in ROM, and 27% had worsened ROM. There was no significant difference in mean VAS scores of patients with improved, unchanged, or worsened ROM postoperatively (3.0 vs 2.8 vs 3.0; P = .068). There was no significant difference in mean VAS scores of patients who developed a soft tissue contracture or required MUA vs those who did not develop these complications (2.7 vs 2.9; P = .24). Similarly, no significant relationship with these outcomes was identified when maximum and discharge VAS scores were analyzed.ConclusionComparable ROM and rates of MUA based on in-hospital pain levels were observed in this large series of primary TKA patients. While significant early pain may limit participation in ROM exercises initially, this does not appear to have a marked impact on ROM-related complications for most patients.Level of EvidenceIII, Therapeutic.     

Enhanced conditioned inhibition following repeated pretreatment with d-amphetamine

We have shown that prior repeated exposure to d-amphetamine facilitates appetitive Pavlovian conditioning. However, animals sensitised in this manner also show elevated levels of stimulated activity. To investigate whether enhanced conditioning was dependent upon increased activity, a conditioned inhibition task was employed in the present study. Rats received d-amphetamine (2 mg/kg, IP) or vehicle once per day for 7 days. After a 7-day drug-free period, an activity assay confirmed that repeated d-amphetamine treatment markedly elevated the locomotor response to a subsequent challenge with 0.5 mg/kg d-amphetamine. Conditioning began 6 days later. In phase 1, stimulus A+ (light or tone) immediately preceded sucrose availability (excitatory conditioning). In phase 2, sucrose again was presented after A+ alone, but not after presentation of a compound of A+ with a second stimulus (AB−). Sensitisation enhanced the acquisition of conditioned approach behaviour to the excitatory stimulus A+ in phase 1. Furthermore, acquisition of conditioned inhibition to the stimulus compound, AB−, was also facilitated. Thus, sensitised rats showed reduced levels of responding to the stimulus compound far sooner than controls. Finally, a retardation test was carried out in stage 3, in which the inhibitory stimulus B- was paired alone with sucrose reward. Sensitised rats initially showed retarded acquisition of excitatory conditioned responding relative to controls, suggesting that B possessed stronger inhibitory associations in these animals. However, sensitised animals again exhibited higher levels of responding in later sessions, consistent with the enhanced excitatory conditioning shown in phase 1. These findings suggest that prior repeated d-amphetamine enhanced the acquisition of inhibitory and excitatory Pavlovian associations; a propensity not readily attributable to stimulated locomotor hyperactivity. Received: 29 December 1997/Final version: 21 July 1998     

Metastases to the thyroid gland: the Royal Marsden experience.

AIM: A review of patients seen at the Royal Marsden Hospital with metastases to the thyroid gland. METHOD: Experience reported on 15 patients that were seen at our institution between 1985 and 2002. RESULTS: The most common site of origin was the kidney (4/15). Ages ranged between 26 and 76 years. Twelve presented with a neck mass. Most had metastatic disease elsewhere at the time of presentation (9/15). Diagnosis was made by fine needle aspiration cytology (5), tru-cut biopsy (1), or surgery (9); surgery comprised total thyroidectomy (3), subtotal thyroidectomy (3) or lobectomy (3). Radiotherapy resulted in disease stabilisation in three patients. Chemotherapy was used to treat local recurrence in two patients post-operatively. The interval from diagnosis of the primary tumour to thyroid metastasis varied from 0 months to 15 years. Thyroid gland metastasis was the initial manifestation of metastatic disease in five patients. Five patients are alive, with one disease free 7 years following resection of the thyroid metastasis. CONCLUSIONS: Thyroid metastases are clinically rare, with the kidney the most common primary site of origin. They usually occur when there are metastases elsewhere, sometimes many years after diagnosis of the original primary tumour. Surgical resection of an isolated metastasis may result in prolonged disease-free survival. Radiotherapy and chemotherapy may be of value in specific situations.