Biomedical subjects
Publications and source records attributed to P Roberts.
Tattoo removal from the forearm often requires excision and split skin grafting. The authors propose the use of a bloodless field to facilitate accurate dermal peeling, to ensure complete removal of the pigment, and to reduce operative time.
Over a 16-year period, 135 custom-made distal femoral prostheses, based on a fully constrained Stanmore-type knee replacement, were used in the treatment of primary malignant or aggressive benign tumours. Survivorship analysis showed a cumulative success rate of 72% at five years and 64% at seven years. Intact prostheses in 91% of the surviving patients gave good or excellent functional results. Deep infection was the major complication, occurring in 6.8% of cases; clinical aseptic loosening occurred in 6.0%. Revision surgery was carried out for loosening and infection, and the early results are encouraging. We conclude that prosthetic replacement of the distal femur can meet the objectives of limb salvage surgery.
A new approach to the hip is described that allows better exposure for difficult revision surgery without the need for trochanteric osteotomy. A V-shaped myofascial flap consisting of the proximal part of vastus lateralis and its fascia with gluteus medius and minimus, is reflected off the greater trochanter and proximal femur giving access to the entire capsule of the hip. If the leg has been significantly lengthened by the revision procedure, abductor tension can be adjusted at closure by altering the reattachment of the flap, analogous to a V-Y-plasty.
The serum levels of tumour marker CA 125 were measured in 162 patients with various digestive tract malignancies and in 155 patients with benign digestive tract diseases. The highest frequency of elevated CA 125 values (greater than 35 U ml-1) was found in patients with liver cancer (78%), but the level was equally often elevated in liver cirrhosis (78%). Two-thirds of the patients with biliary tract cancer had an increased CA 125 concentration, while four patients with benign biliary diseases had an elevated value. The serum level of CA 125 was elevated in only 20% of 60 patients with primary colorectal cancer, and in none of those with local disease (Dukes A or B). The CA 125 concentration seldom increased in patients with recurrent colorectal carcinoma. Twenty-three per cent of 44 patients with gastric cancer had an elevated CA 125 value. Two of 33 patients with benign colorectal and one of 68 patients with benign gastric diseases had an increased CA 125 concentration. The serum values of CA 125 showed no correlation with those of tumour markers alphafetoprotein (AFP), carcinoembryonic antigen (CEA) or CA 19-9. AFP was superior to the other markers in the diagnosis of liver diseases, while CA 19-9 showed the greatest accuracy in gastric diseases. In colorectal diseases, CEA had a higher sensitivity, but a lower specificity than CA 125 and CA 19-9. CA 125 and CA 19-9 had similar sensitivities for biliary tract cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
1. Seven patients clinically diagnosed as being hypersensitive to carbamazepine and one patient hypersensitive to both carbamazepine and oxcarbazepine have been identified. They have been compared with a control group (hereafter referred to as 'control subjects') comprising five patients on chronic carbamazepine therapy without adverse effects and 12 healthy volunteers who have never been exposed to anticonvulsants. 2. An in vitro cytotoxicity assay employing mononuclear leucocytes as target cells has been used first, to determine the ability of 10 different human livers to bioactivate carbamazepine to a cytotoxic metabolite, and secondly, to compare the cell defences of carbamazepine-hypersensitive patients and control subjects to oxidative drug metabolites generated by a murine microsomal system, using a blinded protocol. 3. With human liver microsomes, the metabolism-dependent cytotoxicity of carbamazepine increased with increasing microsomal protein concentration. At a protein concentration of 2 mg per incubation, the cytotoxicity of carbamazepine with human liver microsomes (n = 10 livers) increased from 7.2 +/- 0.8% (baseline) to 16.4 +/- 2.1% (with NADPH; P = 0.002). 4. In the presence of phenobarbitone-induced mouse microsomes and NADPH, the mean increase in cytotoxicity above the baseline with carbamazepine was significantly greater (P less than 0.001) for the cells from the carbamazepine-hypersensitive patients (7.9 +/- 0.8%) than from control subjects (2.6 +/- 0.3%). 5. In the presence of phenobarbitone-induced mouse microsomes and NADPH, there was no significant difference in cytotoxicity between the cells from carbamazepine hypersensitive patients and from control subjects in the presence of either phenytoin or oxcarbazepine.(ABSTRACT TRUNCATED AT 250 WORDS)
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This study was undertaken to determine the appropriateness of celiotomy in 100 consecutive patients who underwent celiotomy solely because of positive diagnostic peritoneal lavage (DPL) following blunt (B) or stab (S) abdominal trauma. A total of 32 (32%) patients had positive DPL by laboratory criteria: blunt trauma: greater than 100K RBC/mm3, greater than 500 WBC/mm3; stab trauma: greater than 50K RBC/mm3, greater than 250 WBC/mm3. DPL in 68 patients was positive by gross inspection; 18 of these 68 patients' DPL laboratory results returned after surgery and did not satisfy the laboratory definition of positive DPL. In all 61 per cent underwent therapeutic celiotomy (TC) and 39 per cent underwent nontherapeutic celiotomy (NTC). Grade I and II spleen and/or liver injuries led to 79 per cent of NTCs. Positive DPL, determined by gross inspection or by laboratory testing, has a very poor accuracy rate when evaluated in light of evolving beliefs that promote nonoperative therapy for grade I and II liver and spleen injuries. When positive DPL is the sole indication for celiotomy in patients with blunt or stab abdominal trauma, an unacceptably large number of NTCs will be performed. DPL should have a limited role in the evaluation of patients with abdominal trauma.
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The effects of enzyme induction on the generation of cytotoxic metabolites from phenytoin, mianserin, imipramine, desipramine and amitriptyline by mouse liver microsomes has been investigated and then compared with the bioactivation mediated by human hepatic microsomes. Cytotoxicity was assessed by co-incubation of drug and microsomes with human mononuclear leucocytes which served as target cells. Enzyme induction was assessed by measurement of hepatic cytochrome P-450 content, and determination of alkoxycoumarin O-dealkylase activity. None of the compounds investigated were metabolized to cytotoxic metabolites in the presence of control mouse microsomes. However, significant bioactivation could be observed for each drug when incubated with microsomes prepared from mice pretreated with either phenobarbitone (60 mg/kg) or beta-naphthoflavone (75 mg/kg). The rank order for metabolism-dependent cytotoxicity with phenobarbitone-induced mouse microsomes (expressed as % cell death) was phenytoin (14.6%) greater than desipramine (10.5%) greater than imipramine (7.5%) greater than mianserin (3.4%) greater than amitriptyline (3.1%). Expression of cytotoxicity with phenytoin required pre-exposure of the target cells to trichloropropane oxide, an opoxide hydrolase inhibitor. Only mianserin and desipramine were activated to cytotoxic metabolites by human liver microsomes. Analysis of stable metabolites revealed that mianserin underwent extensive (greater than 80%) metabolism by both control and induced mouse microsomes and that the principal metabolites, 8-hydroxymianserin, desmethylmianserin and mianserin N-oxide, were the same as those produced by human liver microsomes. These data suggest that mianserin is activated to a cytotoxic metabolite selectively by a constitutive form of human cytochrome P-450, whereas phenytoin, amitriptyline and imipramine are selectively activated by forms of mouse cytochrome P-450 which are induced by either phenobarbitone or beta-naphthoflavone.
Woodchucks (Marmota monax) normally experience gonadal recrudescence towards the end of a 4-5 month hibernation, emerge in late winter, immediately breed in a short 3-week breeding season, and have regressed gonads before the next hibernation. Our studies of wild and captive animals show that fertile females give birth to single litters after a 32-day gestation and their breeding season is terminated by a reactivation of the corpora lutea of pregnancy for 1-3 months immediately postpartum. In nonbred females the breeding season is likewise terminated by spontaneous luteinization of the ovaries for 1-3 months shortly after the vernal equinox. Tests regress and testosterone declines during and after the breeding season. Circannual reproductive cycles persist in the absence of hibernation and are shortened to 9-10 months after 3-5 years of a 12L:12D photoperiod. Unique aspects of this species that merit endocrine investigation include descent/retraction of testes, transient luteolysis at parturition, superactivation of postpartum corpora lutea, regulation of the pituitary-gonadal axis by an annual endogenous metabolic cycle entrained to the annual change in photoperiod, and the hormonal basis of hibernation.
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Traditional formulas, such as the Harris and Benedict equation (HBE), do not accurately predict energy expenditure (EE) in mechanically ventilated, critically ill patients (MVCIP). The purpose of this study was to develop a predictive EE equation to assess EE requirements in MVCIP. A portable metabolic cart was used to measure indirectly EE in 112 MVCIP. Patients were studied at rest and for 30 min on the first or second day of ICU admission. No nutrition was received during the study period. Variables investigated were: age, BSA, Acute Physiology and Chronic Health Evaluation (APACHE II) score, sepsis score, Injury Severity Score (ISS), respiratory rate (f), tidal volume (VT), minute ventilation, mean arterial pressure, heart rate, body temperature (Temp), and outcome. Patient age, APACHE II score, sepsis score, ISS, and BSA were 50 +/- 20 yr, 16 +/- 7, 11 +/- 6, 32 +/- 14, and 1.80 +/- 0.27 m2, respectively. Correlation and multiple regression analyses were used with EE as the dependent variable. A predictive equation (EE [kcal/day] = 945 BSA -6.4 age + 108 Temp + 24.2 f + 817 VT -4349) was determined from variables that contributed greater than 3% to the variance of EE: BSA (52%), age (10%), f (5%), VT (5%), and Temp (3%). The HBE underestimated measured EE by 34 +/- 19% and in 79 patients deviated greater than 15%. Using the new equation, only 15 patients' EE deviated greater than 15% from measured EE. The new predictive EE equation can accurately assess EE in MVCIP.
1. A two compartment system, comprising two adjacent teflon chambers separated by a semi-permeable membrane, has been devised with which to investigate the generation of drug metabolites that are toxic to human cells in vitro. 2. Compartment A contained a drug-metabolising system (human liver microsomes +/- NADPH) and compartment B contained target cells (human mononuclear leucocytes). The semi-permeable membrane retained protein (m.w. greater than 10,000) but allowed equilibration (within 1 h) of drug and drug metabolites, during which time cells remained viable. 3. Incubation of dapsone (100 microM) with human microsomal protein (2 mg ml-1) and NADPH (1 mM) in compartment A caused cell death (8.7 +/- 1.8%) in compartment B, which was reduced significantly (P less than 0.05) by the addition of glutathione (500 microM). Dapsone in the absence of NADPH was not cytotoxic. 4. Chemical analysis showed the presence of dapsone hydroxylamine as the only stable metabolite in both compartment A (5.2 +/- 0.4% incubated drug) and compartment B (3.5 +/- 0.5%). 5. Irreversible binding of dapsone to cells was significantly (P less than 0.05) reduced by omission of NADPH (85 +/- 13 pmol/10(6) cells) or addition of glutathione (103 +/- 9) compared with control values (153 +/- 51).
A retrospective analysis of 53 consecutive cases of orchidopexy performed at the British Military Hospital Munster between 1984 and 1988 showed that the average of referral for orchidopexy was 4 years 7 months and that the average age at surgery for mal/un-descended testes was 5 years exactly. Sixty-four percent of all orchidopexies were carried out before the age of 5 years; 8 percent were carried out by the age of 2 years.
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The orthopaedic scooter is an alternative to crutches. It gives the patient greater freedom on level smooth surfaces and uses less energy.
The activation time of endothelial cells and myogenic cells (presumptive satellite cells) in small skeletal muscle transplants was examined, as well as in the muscle bed underlying the transplants, using autoradiography and light microscopy. At varying intervals, from 12 to 336 hours (14 days) after transplantation, the transplants and some of the underlying muscle were removed from two or four mice (at each interval), after the injection of each animal with tritiated thymidine 1 hour prior to transplant removal. Thus premitotic cells synthesising DNA were labelled. Only one labelled endothelial cell nucleus was seen in all 20 transplants examined during the first 60 hours. Contrastingly, labelled endothelial nuclei were plentiful in muscles underlying the transplants from 36 hours post-transplantation. There was no evidence of a functional vascular supply in the transplants until 72 hours when one of the eight transplants examined at this time showed very slight peripheral revascularisation, with these peripheral vessels containing labelled endothelial cell nuclei. Ninety six hours after transplantation half the transplants sampled showed peripheral revascularisation, with these vessels containing labelled nuclei, and by 120 hours all transplants showed functional blood vessels and contained labelled endothelial cell nuclei. By 14 days after transplantation revascularisation and myogenesis were complete with only an occasional labelled nucleus seen. Autoradiographically labelled premitotic muscle nuclei (presumptive satellite cells) were observed in transplants from 48 hours after transplantation. These results show that revascularisation of the transplanted muscles is not necessary for the activation of myogenic cells, but that activation is probably due to some other stimulus, possibly the diffusion of nutrients from blood vessels of the adjacent tissues.