Biomedical subjects
Publications and source records attributed to M Palmer.
The results of a double blind crossover comparative trial of the nonsteroidal antiinflammatory drug tiaprofenic acid with placebo in the treatment of rheumatoid arthritis are reported. Tiaprofenic acid was confirmed as being an effective drug of this class and no untoward side effects were encountered. Individual response was varied and not related to disease activity.
To investigate the effect of needle size and number of passes into a tumour mass on the cell yield from a fine needle aspirate, an in vitro study was undertaken in 19 consecutive tumours removed surgically for biopsy. Different needle sizes (23G, 21G, 19G) passed in random order, five, ten and fifteen times into the tumours, were compared. The type of tumour, needle size and number of passes independently and significantly influenced cell yield. A 21G(green) needle passed into the tumour at least 10 times was the most efficient in obtaining cells. This in vitro study could explain the variation in the reported accuracy of fine needle aspiration cytology from groups using different techniques and is perhaps one reason why the highest diagnostic accuracy and the lowest rate of unsatisfactory aspirates comes from a centre which uses a 21G needle and at least 10 passes through the tumour.
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Control of abnormal posturing is a challenge in the care of severely head-injured adults and must be a component of care in both critical care and acute rehabilitation stages of recovery. Severe head injury is indicated by a Glasgow Coma Scale rating of eight or less for at least six hours post-injury. Long-term disabilities are common among survivors, mostly men under 40 years of age. This paper examines the pathophysiology of abnormal posturing and positioning and handling techniques to prevent and/or control abnormal motor activity. The effect of positioning on intracranial pressure is also discussed.
Prospective monthly magnetic resonance imaging (MRI) studies were done over 6 months in seven relapsing MS patients. MRI and neurologic evaluations were compared for sensitivity in detecting disease activity. Four patients were clinically stable throughout the study. Three patients had five clinical relapses, two localized to the spinal cord and three to the brainstem. Eighteen new and ten enlarging MRI lesions were seen in five patients. Most lesions were less than 10 mm in diameter. All were clinically silent. Two patients developed major enlarging MRI lesions (seen in three slices) which increased in size over 2 months and then gradually became smaller over 2 months, leaving behind small residual areas of abnormality. There were 36 follow-up scans, 17 of which (47%) showed evidence for increasing activity. Thirteen (36%) of the scans had new lesions, most of them being small. This study shows that MRI evidence for disease activity in MS is much more frequent than is clinical evidence.
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Group B streptococcal infection may result in significant morbidity and mortality in both infants and adults. The experience with group B streptococcal disease was analyzed at one medical center over a ten-year period from 1975 to 1984. Streptococcus agalactiae bacteremia was observed in 29 adults and 26 infants, with an attack rate of 0.2 cases per 1000 adult admissions and 3.2 cases per 1000 live births, respectively. The majority of adult infections apparently occurred as a result of nosocomial acquisition and was associated with a high mortality rate of 38%. Risk factors for group B streptococcal sepsis in adults include diabetes mellitus, malignancy, and hepatic failure. The majority (73%) of neonatal cases occurred within seven days of birth and occurred in a setting of maternal fever, prolonged rupture of membranes, or prematurity. The mortality rate in infants was remarkably low at only 15%. Fatalities occurred in both adults and infants, despite appropriate antimicrobial therapy. Infection control strategies against group B streptococcus must address potential nosocomial dissemination in adults as well as vertical transmission in infants.
172 persons with mild to moderate hypercalcaemia were followed up for 14 years. Life-table analyses showed that, among persons aged 70 years or less at the time of detection of the hypercalcaemia, survival was lower in the hypercalcaemic group than in a normocalcaemic age and sex matched control group. No such difference was found among older persons. The lower survival was related to degree of hypercalcaemia, and this held true when systolic and diastolic blood pressure, serum glucose, serum uric acid, and serum cholesterol were taken into account in a multivariate analysis. The lower survival seemed to be due mainly to deaths from diseases of the circulatory organs. No person with normal renal function at the beginning of the study period had a more than marginally raised serum creatinine at follow-up.
Patients with multiple sclerosis (MS) frequently develop psychiatric disturbances. The clinical histories and magnetic resonance imaging results from eight patients with MS and psychiatric disorders were compared with those from eight control MS patients matched for age, sex, duration and severity of illness, and clinical course. Both groups had widespread lesions on the magnetic resonance imaging scans; however, the psychiatric group had more clinically defined sites of MS involvement, possibly indicating a difference in the biologic activity of the lesions in this group. The total lesion area was not different between the groups. However, the distribution of lesions did differ; the psychiatric group had significantly more temporal lobe involvement than the control group. These results indicate a role for the cerebral lesions themselves, particularly those in the temporal lobes, in the genesis of psychiatric disorders in MS.
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One hundred seventy-three patients with multiple myeloma were treated from the time of diagnosis with standard oral melphalan and prednisone at 28-day intervals until they became refractory to treatment. Response to treatment was determined according to the Chronic Leukemia-Myeloma Task Force (TF) criteria, and independently according to the Southwest Oncology Group (SWOG) criteria. Survival by disease stage and response according to the two sets of criteria were analyzed for patients living longer than 3 months. The median survival of responding and nonresponding (TF criteria) stage II patients was 43.8 and 40.3 months, respectively (P = .29). By SWOG criteria, median survival for responding and nonresponding stage II patients was 48.3 and 39.0 months, respectively (P = .12). In stage III patients, median survival for responders and nonresponders (TF criteria) was 34.0 and 21.7 months, respectively (P = .01), compared with 35.5 and 24.4 months (P = .04) by SWOG criteria. These data would suggest that the TF criteria predicts a survival disadvantage only in very advanced myeloma and that applying the stricter limits for the definition of response of the SWOG does not further aid in selecting a subgroup of myeloma patients with poorer survival.
To quantify the risk of radiation-induced leukemia and provide further information on the nature of the relationship between dose and response, a case-control study was undertaken in a cohort of over 150,000 women with invasive cancer of the uterine cervix. The cases either were reported to one of 17 population-based cancer registries or were treated in any of 16 oncologic clinics in Canada, Europe, and the United States. Four controls were individually matched to each of 195 cases of leukemia on the basis of age and calendar year when diagnosed with cervical cancer and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not increased [relative risk (RR) = 1.03; n = 52]. However, for all other forms of leukemia taken together (n = 143), a twofold risk was evident (RR = 2.0; 90% confidence interval = 1.0-4.2). Risk increased with increasing radiation dose until average doses of about 400 rad (4 Gy) were reached and then decreased at higher doses. This pattern is consistent with experimental data for which the down-turn in risk at high doses has been interpreted as due to killing of potentially leukemic cells. The dose-response information was modeled with various RR functions, accounting for the nonhomogeneous distribution of radiation dose during radiotherapy. The local radiation doses to each of 14 bone marrow compartments for each patient were incorporated in the models, and the corresponding risks were summed. A good fit to the observed data was obtained with a linear-exponential function, which included a positive linear induction term and a negative exponential term. The estimate of the excess RR per rad was 0.9%, and the estimated RR at 100 rad (1 Gy) was 1.7. The model proposed in this study of risk proportional to mass exposed and of risk to an individual given by the sum of incremental risks to anatomic sites appears to be applicable to a wide range of dose distributions. Furthermore, the pattern of leukemia incidence associated with different levels of radiation dose is consistent with a model postulating increasing risk with increasing exposure, modified at high doses by increased frequency of cell death, which reduces risk.
The natural history and prognostic factors of primary sclerosing cholangitis (PSC) are poorly defined. We reviewed our experience with PSC to determine its natural history and whether any factors on presentation or during follow-up were indicative of a favorable or unfavorable prognosis. Thirty-eight patients were followed up for 75.1 +/- 58.7 months; 17 (45%) had a poor outcome, defined as the occurrence of death (11 patients [29%]), variceal hemorrhage, hepatic encephalopathy, or hepatic transplantation. We found the following: the rate of progression of PSC is highly variable; an asymptomatic presentation may not indicate a more favorable outcome or prolonged survival; a serum bilirubin value of four times or more the upper limit of normal, particularly if sustained so as to exclude a reversible cause, is indicative of late-stage disease with a likelihood of subsequent poor outcome and death; and variceal hemorrhage may occur before the terminal stage of the disease.
Metaphit (1-[1-(3-isothiocyanatophenyl)-cyclohexyl]piperidine), a derivative of the psychotomimetic drug phencyclidine (PCP), is postulated to bind irreversibly to PCP receptors. We examined here the electrophysiological interactions of metaphit with PCP in rat cerebellar cortex, since a specific effect of PCP on cerebellar neuronal circuitry has been shown. Metaphit, applied locally to Purkinje neurons by micropressure ejection through multibarreled micropipettes, has a reversible depressant action lasting for 5-20 min. Following this, PCP-induced inhibition is blocked with no recovery despite repeated applications of PCP for over an hour. This blockade was not seen unless the dose of metaphit was sufficient to transiently depress Purkinje neuron discharge. Metaphit does not antagonize inhibitory effects of locally applied norepinephrine or gamma-aminobutyric acid. This electrophysiological data suggests that metaphit is an irreversible antagonist of PCP in the cerebellum.
The presence of lipid storage was demonstrated in type C Niemann-Pick disease by histopathologic and ultrastructural studies. Pleomorphic membranous inclusions, with variable proportions of light and dark granular material, were observed within the conjunctival fibrocytes, endothelial cells and pericytes, keratocytes, lens epithelium, retinal ganglion cells, retinal pigment epithelium, fibrocytes in the uveal tract, and optic nerve fibrous astrocytes. Only optic nerve and retinal ganglion cell involvement had clinical counterparts represented by optic nerve pallor and perimacular gray discoloration.
The concentration of radioactivity in the breast milk of four nursing mothers who had received injections of 99mTc macroaggregated albumin (MAA) was measured. The results were compared with previous measurements, and an estimate of the radiation dose to an infant from internal and external sources was obtained for various times of recommencement of breast feeding. It is suggested that feeding can recommence earlier than the normally recommended 24 h if this is thought to be clinically desirable.
The coypu (Myocastor coypus Molina) is an aquatic rodent that has become a widespread pest in the south-east of England. Since the natural habitat of this animal is aquatic, the possibility of infection with leptospires was investigated. Twenty-nine coypu were trapped and examined by serological, histological and cultural methods. Of these, there was serological evidence of infection in seven coypus and Leptospira interrogans var. Wolffii was isolated from a further animal. This appears to be the first report of the isolation of leptospira from a coypu in Great Britain.