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Biomedical subjects
Publications and source records attributed to D Pritchard.
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This study examines the ability of patients to estimate how long they need to spend with the doctor. It investigates the effect of a patient making such an estimate on his or her satisfaction with the consultation and participation in the doctor-patient relationship.
Acquired cold urticaria with a negative cold stimulation test has been described in seven patients in whom the standard ice cube test did not induce localized urticaria. Subsequent total body cold exposure induced a generalized urticaria. A patient with this syndrome is presented where blood histamine levels rose from 9 to 60 micrograms/dL after a negative local cold stimulation test and from 60 to 90 micrograms/dL after total body cold exposure. Urticaria occurred only after generalized cold exposure. Blood histamine levels following the ice cube test may represent a sensitive method to diagnose this form of atypical acquired cold urticaria, without subjecting the patient to the risk of anaphylaxis reported following total body cold exposure.
Two Pediatric Intergroup Ewing's Sarcoma studies of patients with metastatic disease (IESS-MD) have used multimodal therapy consisting of intensive combination chemotherapy and radiation therapy (XRT) to areas of gross disease detected at the time of diagnosis. In IESS-MD-I, conducted from 1975 to 1977, 53 eligible patients were entered and received the chemotherapeutic agents vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, and dactinomycin with concomitant XRT (VACA + XRT). In IESS-MD-II, conducted from 1980 to 1983, 69 eligible patients were entered and received 5-fluorouracil (5FU) in addition to the chemotherapeutic agents of IESS-MD-I; initial intensive chemotherapy was given and XRT was delayed until week 10 (VACA + 5FU, delayed XRT). The best response rate (complete and partial remissions combined) was 73% in IESS-MD-I and 70% in IESS-MD-II, so there was no statistical evidence of a difference in response rates (P = 0.62). The length of best response also was similar between studies (P = 0.79), with approximately 30% of the patients on both studies remaining in remission at 3 years. The percentage of patients surviving 5 years or more was 30 on the first study and 28 on the second study (P = 0.49). The major sites of relapse after a response were lung and bone, each occurring with nearly equal frequency. The age of the patient was related to both best response rate and survival: patients 10 years of age or younger had substantially higher response and survival rates than patients 11 years of age or older. The favorable prognosis for younger patients might be explained by a more favorable distribution of primary sites at diagnosis; 39% of patients 10 years of age or younger had rib primary sites, compared with only 16% for patients older than 10 years of age (P = 0.05). The frequency of life-threatening toxicity was substantially higher in IESS-MD-I (30%) than in IESS-MD-II (9%), but the frequency of fatal toxicity was similar (6% to 7%). Fatal complications included Adriamycin-induced cardiomyopathy, Pneumocystis carinii pneumonia, unspecified pneumonitis, and sepsis. The most common toxicity and complications were leukopenia and infections.
Rats treated with temelastine (SK&F 93,944), a novel histamine H1-receptor antagonist, develop thyroid lesions characterized by hypertrophy and colloid depletion. To investigate the mechanism underlying the lesion the biliary clearance and hepatocellular accumulation of radio-labelled iodothyronines was measured in rats or cultured rat hepatocytes. Treatment with temelastine increased both the biliary clearance (approximately 300% of control) and hepatocellular accumulation (approximately 200%) of thyroxine (T4) but had little or no effect on tri-iodothyronine (T3). Chromatographic analysis of bile samples from temelastine-treated rats showed that the majority (approximately 78%) of T4 was present in the unconjugated form. This contrasted with data from phenobarbitone-treated rats which showed that approximately 80% of T4 in the bile was present as the glucuronide conjugate. Studies with cultured hepatocytes showed that the hepatocellular accumulation of T4 was energy dependent. At 4 degrees C the treatment-related increases in accumulation of T4 were abolished, suggesting that temelastine is specifically affecting the high affinity, energy dependent system which preferentially transports thyroxine into hepatocytes. Because temelastine is metabolized extensively, investigations were undertaken to discover if the hepatic effects were caused by the parent compound or an oxidative metabolite. The results showed that the hepatocellular accumulation of T4 remained increased in hepatocytes co-incubated with temelastine and 1-aminobenzotriazole (a suicide inhibitor of cytochrome P450), even though no measurable P450 could be found in the cells. Also, in studies with two major "rat" metabolites of temelastine, i.e. 93,944-Met I or 93,944-Met VIII, treatments failed to reproduce the responses seen with the parent compound.(ABSTRACT TRUNCATED AT 250 WORDS)
Twenty-three volunteer subjects were compared with 23 (matched) control subjects on self and parental ratings of anxiety, depression, shyness-sensitivity, sleeping difficulties, perfectionism, psychosomatic problems (unrelated to headache), other behavioural disturbances, major life stress events and parental expectations (i.e. achievement orientation). Results indicated that the headache children showed significantly higher shyness-sensitivity, psychosomatic problems and behavioural disturbances and significantly lower parental expectations than the control group children. No other differences were found. While none of the variables were predictive of the frequency or intensity of head pain, measures of anxiety, perfectionism, and life stress events contributed significantly to the prediction of the severity of head pain.
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The administration of SK&F 93479, a novel histamine H2 antagonist, to Wistar rats has been shown to produce thyroid lesions associated with an increased clearance of plasma thyroxine (T4) and elevated plasma TSH concentrations. To determine if these changes were mediated via an increase in the hepatic clearance of thyroid hormones, the biliary clearance and hepatic accumulation of iodothyronines were measured in rats and cultured hepatocytes treated with SK&F 93479. Both the in vitro and in vivo results showed that treatment with SK&F 93479 caused an increased hepatic accumulation (approx. 200% of control) and biliary excretion (2-3-fold control values) of T4 but had little or no effect on T3 uptake. The in vitro studies showed that the treatment related increase in hepatic thyroxine accumulation was temperature and therefore probably energy dependent, while inhibition of cytochrome P-450 dependent enzyme activity did not alter the accumulation of T4 suggesting that the parent compound and not some oxidative metabolite was responsible for the hepatic effects. Chromatographic analysis of bile from SK&F 93479 and phenobarbitone-treated rats showed that in the latter animals 81% of the T4 was present as the glucuronide conjugate (consistent with enzyme induction) whereas in the SK&F 93479-treated rats only 25% was present as the conjugate with 75% being in the unconjugated form. These studies show that SK&F 93479 increases the hepatic accumulation and biliary clearance of T4 by a novel mechanism not associated with liver microsomal enzyme induction.
Eighteen patients had prosthetic proximal humeral replacement with either a metal or ceramic prosthesis. Three replacements were performed for fracture nonunions, five for benign neoplasms, six for low-grade malignancies, and four for high-grade malignancies. Retention of elbow and hand function was good. In five of the 11 ceramic prostheses, failure occurred at the humeral-prosthetic junction even though it was designed for biologic fixation. Ten of 18 prostheses subluxated or dislocated. Twelve of 18 patients have had revision operations. While the revision rate in this initial series was high, valuable experience was gained for further investigations of shoulder arthroplasty.
We have investigated the opsonic and protective effects of fibronectin (FN) against type III group B streptococci. When used by itself, the FN failed to promote actual internalization of group B organisms. The addition of FN to group B streptococci that had been preopsonized in an immunoglobulin preparation modified for intravenous use ( IgIV ) or a type-specific, murine monoclonal antibody of IgG isotype markedly enhanced interaction with human polymorphonuclear leukocytes (PMN). A similar enhanced effect was observed when the FN was combined with type-specific monoclonal antibody preparations of IgM and, surprisingly, IgA isotype. Preincubation experiments indicated that the major effect was upon the PMN rather than directly on the bacteria, but we could not demonstrate an effect of FN on cell surface receptors for the Fc fragment of Ig or C3b using rosetting techniques. In addition to enhancing the in vitro opsonic activity of Ig, the FN significantly increased the protective effect of the polyclonal and monoclonal Ig preparations in an animal model of neonatal group B streptococcal disease. Thus, FN appears to have a critical role in the host defense mechanisms against group B streptococci.
The deep cortex of the lymph node of various species actually consists of hemispherical structures, termed deep cortex "units." Each unit is centered under an opening of an afferent lymphatic and comprises a center and a periphery. In a recent work on the nude mouse, we found that the congenital athymic state inhibits the development of the lymphocyte population in the center of the units as well as in a related area of peripheral cortex, and that it also modifies other nodal components. In the present work, we wanted to compare the effects of the athymic state on the rat nodes. Therefore, nodes from various anatomical locations in 8-week-old nude rats were submitted to a tridimensional analysis. The overall effects of the congenital athymic state were found to be comparable in rats and mice. However, marked differences were noticed in the modifications of the node histology, in both species of nude animals. Their significance is discussed together with new findings.
A series of 17 long bone defects following tumor resections were reconstructed using titanium fiber metal implants with adequate bone grafts. There were nine diaphyseal segmental arthroplasties and eight arthrodeses of the knee. The results were excellent in 11 and satisfactory in five, and there was one failure. Sixteen patients became fully weight-bearing. Adequate bone grafts, especially from both posterior iliac crests, and good skin coverage are essential to adequate bony reconstruction.
Forty-four patients with metastatic (36 patients) and advanced regional (eight patients) Ewing's sarcoma were treated on a protocol employing intensive combination chemotherapy and radiotherapy to all sites of overt disease (primary site and metastatic sites). Thirty-one patients achieved a complete remission, eight achieved a partial remission, and five patients did not respond to treatment. Of the 31 patients who achieved a complete remission (12 had metastases and six had regional spread), 18 remained disease-free with a median follow-up of 34 months, while recurrences occurred in nine patients. Four patients died of complications of treatment. Although late relapses can still be expected, it appears that intensive multimodal management in metastatic Ewing's sarcoma can produce prolonged disease-free survival and possibly cure in a significant percentage of patients.
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A case of eumycotic mycetoma with lesions in the skin, nasal cavity and lymph nodes of a cow is reported. The case history, clinical course, macroscopic and microscopic appearance of lesions, and fungal isolation are described. Drechslera rostrata was isolated from pathological tissue and Koch's postulates were satisfied on mouse inoculation. This is the first infection of its type recorded in Australia and features contrasting with cases reported in other countries are discussed.
2 years of experience in the first phase of a large cooperative national hypertension programme yielded data indicating that a good level of patient adherence can be achieved and that satisfactory blood-pressure control can be maintained long term. For 116 participants, all employed persons, dropout in the first year was 20% but only 3% dropped out in the second year. At the second annual examination, 82% of those still in the programme had diastolic pressures under 90 mm Hg, with an average reduction of 18 mm Hg. Thus, nearly two-thirds (64%) of all patients originally enrolled were both active and with normal levels of blood-pressure after two years. Only 18% of active programme-treated patients had diastolic pressure 90 mm Hg or higher at the second anniversary in contrast with 33% of patients referred to their own doctors. In programme-treated patients, standard medication was used; diuretics effectively lowered blood-pressure in a third of patients, and diuretics plus reserpine were effective for another 20%. Special features of the programme included assistance to physicians by health counsellor therapists. Methods for achieving a high adherence-rate and satisfactory blood-pressure control probably have wider applicability.
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