Biomedical subjects
Publications and source records attributed to C Francis.
Two siblings with Senior-Loken syndrome are described. The need for a full evaluation of renal function and hearing in children with a retinal dystrophy is emphasised.
BACKGROUND: Relapse of small cell lung cancer is not usually treated with further chemotherapy as results are considered to be disappointing. METHODS AND RESULTS: Six patients with relapse of small cell lung cancer after a complete initial response and remission of more than one year responded to repeat treatment with the initial chemotherapy comprising carboplatin, etoposide, and epirubicin. The second remission ranged from six months to more than 15 months. CONCLUSION: In patients with a relapse of small cell lung cancer after a complete initial response and prolonged remission retreatment with the initial combination chemotherapy cannot be dismissed and requires further study.
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Intraluminal pH monitoring in man should be performed with disposable multichannel assemblies that allow recordings at multiple sites and prevent transmission of infection. Currently available glass electrodes are unsuitable for this purpose because of their size and price. We have thus constructed and tested a small, combined ion sensitive field effect transistor (ISFET) pH electrode incorporating an integral reference electrode. In vitro studies showed that both ISFET and glass electrodes (440-M4, Ingold, Switzerland) have a linear response over the pH range 1.3-8.0 and that they are comparable with regard to response time and 24 hour drift. Twenty one hour intragastric pH recordings were performed simultaneously in eight healthy volunteers using a glass electrode and an ISFET electrode, placed no more than 2 mm apart in a combined assembly. This was located in the gastric corpus under fluoroscopic control. The 21 hour pH curves recorded by each electrode type showed identical patterns: an early morning rise in pH with three meal-associated pH peaks lasting for about two to three hours. The means of the 21 hour pH medians were 2.09 and 2.07 as measured by the glass and the ISFET electrodes respectively. Thus, ISFETs are suitable for the construction of inexpensive and hence disposable multichannel pH monitoring assemblies of small diameter. Provided that they can be produced in large numbers with appropriate technical support, ISFETs have the potential to replace glass electrodes for long term monitoring of gastrointestinal luminal acidity.
Nuclear magnetic relaxation rates are measured for whole blood, blood plasma, whole blood clots, and plasma clots in vitro. Relaxation rates are linear in the hematocrit and transverse relaxation rates are significantly greater than longitudinal relaxation rates. Longitudinal relaxation rates measured from 0.01 to 42 MHz for proton Larmor frequencies are found to decline monotonically with increasing magnetic field strength; however, the dispersion curves do not follow a simple Lorentzian behavior, which is anticipated in a suspension of particles in a solution of proteins having a distribution of molecular weights. The transverse relaxation rate is a function of the acquisition parameters, in particular, the choice of TE in either Hahn echo experiments or in echo-train experiments. The origin of this dependence of T2 on TE or the interpulse spacing in an echo train is identified with the exchange of water from inside the red blood cell to the outside and is only an important relaxation mechanism in the case where the blood cell membrane is intact and the cell contains deoxygenated hemoglobin. The dependence of the apparent transverse relaxation rate on the interpulse spacing in a Meiboom-Gill-Carr-Purcell pulse sequence provides the estimate that the mean residence time of water inside the blood cell is about 10 ms. These data provide a sound basis for understanding the dependence of magnetic images on magnetic field strength and the choices of the image acquisition parameters, TE and TR.
A case of plasma cell granuloma of the lung is presented, and the clinical, radiological, histological, diagnostic and therapeutic data obtained from 97 published cases are reviewed. Since the disease is usually peripheral, the diagnosis rests on surgical biopsy and histological examination. In the case presented here, it was established on intrabronchial biopsy obtained by fibroscopy.
One hundred thirty-six unselected patients with Crohn's disease (43 men, 93 women) were studied for the possibility of psoriasis and questioned regarding their family history, as were 136 controls, matched for age and sex. Psoriasis was present in 13 of the 136 patients with Crohn's disease (9.6%), compared with three of 136 controls (2.2%) (p less than 0.02). Age at onset and anatomical site of Crohn's disease did not influence the result, and there was no difference between the sexes. Fourteen (three with psoriasis) of the 136 Crohn's patients (10%) had a family history of psoriasis in first-degree relatives compared with four of 136 controls (2.9%) (p less than 0.02). Psoriasis is more common in patients with Crohn's disease and their first-degree relatives than in controls, suggesting the possibility of a genetic link. Psoriasis should be included among the extraintestinal manifestations of the condition.
A multi-center, open trial was conducted to determine the maximal tolerable dose of carboplatin in combination with conventional doses of both etoposide and an anthracycline for the treatment of previously untreated small cell lung cancer (SCLC) patients. Ninety-five patients [48 with limited disease (LD) and 47 with extensive disease (ED)] received a total of 376 courses of treatment. Carboplatin was given on day 1 at a dose of 250 mg m-2 in 60 courses, 300 mg m-2 in 69, 330 mg m-2 in 236 and 350 mg m-2 in 11, with 120 mg m-2 etoposide on days 1, 3 and 5 and either 40 mg m-2 adriamycin or 60 mg m-2 epirubicin on day 1. Epirubicin was not administered before carboplatin reached the dose of 330 mg m-2. Courses were repeated every 3 weeks. The main toxicity was hematological. The first course of therapy induced a dose-dependent decrease of leucocyte, neutrophil and platelet counts: all patients, except one, who received 350 mg m-2 carboplatin had a neutropenia below 200 microliters-1 and a thrombopenia below 100,000 microliters-1. Three patients died of septicemia. Other toxicities were well tolerated. After three courses, patients were re-staged by performing a mandatory fiberoptic bronchoscopy and a thoracic computed axial tomography (CAT). The overall objective response rate for 86 evaluable patients was 91% (98% for LD) with 21% complete remissions (30% for LD). All 23 hepatic and six brain sites, evaluable after chemotherapy alone, responded.(ABSTRACT TRUNCATED AT 250 WORDS)
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The probability that patients with collagen vascular diseases (CVD) will develop fibrosis is unpredictable. Since changes in bronchoalveolar lavage (BAL) cell data can be observed in CVD patients without evidence of lung involvement, we investigated whether the study of soluble components in BAL could help to distinguish CVD patients with lung involvement (n = 15) from those without pulmonary disease (n = 37). Our results demonstrate that the alveolitis observed in patients with overt lung involvement is associated with an increase of BAL alpha 2-macroglobulin (alpha 2-MA). In contrast, the BAL alpha 2-MA levels were found to be normal in CVD patients without evidence of pulmonary disease as well as in CVD patients with overt lung involvement treated with steroids. This was observed even in the presence of high neutrophil or lymphocyte counts in BAL. In conclusion, when neutrophils or lymphocytes accumulate in the lungs of CVD patients without evidence of lung damage, in the majority of patients this cell accumulation is not associated with an increase of BAL soluble components.
Tumour progression is dependent on many factors including antiproteases and proteases released by tumour cells or host cells infiltrating the tumour. In the present study, we evaluated the antiprotease content, namely alpha 2-macroglobulin (A2M) and alpha 1-proteinase inhibitor (A1PI) and neutrophil (PMN) elastase complexed with A1PI, in limited and extended lung cancer patients compared to a nonsmoker and smoker control population. Data showed that A2M and A1PI were increased in the involved lung from limited cancer when compared to normals. In extended lung cancer, A2M content was also increased in the uninvolved side. The concentration of PMN elastase-A1PI complex was increased on both sides in lung cancer patients (10.2 ng.ml-1 in the uninvolved side, 8.2 ng.ml-1 in the involved side) when compared to nonsmokers (1.9 ng.ml-1, p less than 0.001) and smokers (3.8 ng.ml-1, p less than 0.005). This increase was not solely due to the smoking habit. We conclude that antiproteases and PMN elastase complexed with antiprotease are increased in lung cancer area. This increase could result in extracellular changes in lung cancer.
A multicentric randomized prospective trial was conducted to test whether late intensification chemotherapy would increase the remission rate, the relapse-free survival, and the survival of small-cell lung cancer patients responding to induction chemotherapy. Autologous bone marrow transplantation was used as support to reduce the duration of the aplasia induced by very high-dose chemotherapy. As induction chemotherapy, 101 patients received, during a period of 5 months, a total dosage of 120 mg/m2 methotrexate, 4.5 mg/m2 vincristine, 1,800 mg/m2 cyclophosphamide, 180 mg/m2 doxorubicin, 160 mg/m2 cisplatin, 750 mg/m2 VP-16-213, and 30 Gy prophylactic cranial irradiation. Forty-five patients, selected for their sensitivity to this induction treatment, were randomized to a last cycle of chemotherapy that combined cyclophosphamide, BCNU, and VP-16-213 either at a conventional dosage of 750 mg/m2 intravenously (IV), 60 mg/m2 IV, and 600 mg/m2 orally or alternatively at a very high dosage of 6 g/m2 IV, 300 mg/m2 IV, and 500 mg/m2 IV, respectively. In the late intensification group, the complete remission rate increased from 39% before randomization to 79% after high-dose chemotherapy. Median relapse-free survivals after randomization for intensified and control chemotherapy groups were 28 and 10 weeks, respectively (P = .002). Median overall survival after induction therapy was 68 weeks for the intensified group compared with 55 weeks for the conventional therapy group (P = .13). Four patients died during intensification. Patients in both groups relapsed at the primary site. It can thus be concluded that late intensification chemotherapy for sensitive small-cell lung cancer increases the complete remission rate and resulted in a statistically significant increase in the relapse-free survival. However, since relapse occurred at the primary site and toxicity was high, overall survival was not significantly improved.
Pleural fluid lactate (PFL) and blood lactate (BL) concentrations were simultaneously measured in samples from 46 patients with pleural effusion. PFL exceeded 6 mmol/l in all 15 patients with pyogenic bacterial pleurisy but in only 5 of the other 31 patients. We have found that a PFL-BL difference greater than or equal to 6 mmol/l has a sensitivity of 100% and a specificity of 93.8% in detecting pyogenic pleural effusions. Results are available within 1 h of sample collection, so that PFL-BL difference may become a useful aid in the early assessment of pleural effusions.
Endogenous prostaglandin E2 appears to play an important role in cardiovascular homeostasis. When administered exogenously, it is a potent vasodilator, but the requirement for intravenous administration and its short duration of action have limited studies to its acute effects. A novel prostaglandin E2 analogue, CL 115347, can be administered transdermally on a long-term basis. The cardiovascular responses to the chronic administration of CL 115347 were studied in a double-blind, placebo-controlled trial in 26 subjects with essential hypertension (16 given drug, 10 placebo) maintained on a 100-mEq sodium diet. Administration of CL 115347 produced a fall in diastolic blood pressure of 7.8 +/- 1.3 mm Hg, compared with a 2.3 +/- 1.7 mm Hg fall in controls (p = 0.02), with no change in heart rate. The direct vascular effect of the drug was confirmed by attenuation of the vasoconstrictor response to angiotensin II infusion (13.4 +/- 3.1 vs 21 +/- 2 mm Hg at 3.0 ng/kg/min; p less than 0.05). However, the chronic blood pressure effect of CL 115347 was modest. Subjects receiving active drug showed significant compensatory increases in plasma renin, aldosterone, and norepinephrine levels accompanied by sodium retention and kaliuresis. In summary, chronic administration of this prostaglandin E2 analogue resulted in a modest decrease in blood pressure and antagonism of angiotensin II-mediated vasoconstriction. However, its effects were largely offset by compensatory increases in vasoconstrictor hormones and sodium retention.
The concentrations of alpha 2-macroglobulin (alpha 2M), IgM, and the various molecular forms of IgA were measured in unconcentrated bronchoalveolar lavage (BAL) of normal subjects and in that of patients with interstitial lung disease. In BAL of control subjects, as previously observed in other external secretions, orosomucoid-coefficient of excretion relative to albumin (RCE) = 1.1 (albumin RCE = 1)-IgG (RCE = 0.7 in nonsmokers), and alpha 2M (RCE = 0.04) appeared to be secreted mainly by seepage from plasma according to molecular size. The secretion of p-IgA (RCE = 22), IgM (RCE = 0.09), and transferrin (RCE = 1.2) was selective, suggesting either local lung synthesis of these components or their active transepithelial transport. Concentrations of p-IgA, alpha 2M, and IgM in BAL displayed RCE at least 10 times lower than in other external secretions, reflecting the unsignificant local synthesis of these components in alveolar septa. In interstitial lung diseases, including sarcoidosis, hypersensitivity pneumonitis, and other lung fibroses, all protein concentrations in BAL were raised. Increased seepage of plasma proteins across the blood-gas barrier accounted for the elevation of orosomucoid and p-IgA (RCE unchanged). It probably accounted for the appearance in BAL of a characteristic peak of serum type dimeric IgA unbound to secretory component (SC), for the reduced percentage of free SC (5% versus 27% in control subjects), and for part of the increased percentage of m-IgA (52% versus 28% in control subjects). Contribution of local synthesis, presumably by cells infiltrating the alveolar tissue, was indirectly demonstrated for m-IgA and IgG, which were selectively secreted, more than 2-fold greater than albumin.(ABSTRACT TRUNCATED AT 250 WORDS)
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Exercise Physiol. 52: 638-641, 1982) have shown in dogs that airway closure may induce rib cage deformation and nonhomogeneous alveolar pressure swings, and they have suggested that this could lead to thoracic gas volume (TGV) overestimation by body plethysmography. However, in humans the rib cage is less easy to distort than in dogs. In four healthy volunteers we measured TGV by plethysmography before (B) and during (D) the occlusion of the middle and lower right lobes by a balloon (attached to a double-lumen catheter) positioned in the intermediate right bronchus. Subjects were trained to perform panting maneuvers preferentially with intercostals and accessory muscles or the diaphragm. Five to eleven TGV measurements were made in each subject with each panting pattern B and D occlusion. Balloon inflation resulted in no change in TGV whether low [13.3 +/- 3.4 (SD) cmH2O] or high (46.8 +/- 8.4 cmH2O) transdiaphragmatic pressures (Pdi) were used: TGV 4.0 +/- 0.4 (B) vs. 4.0 +/- 0.4 liters (D) and 4.3 +/- 0.4 (B) vs. 4.3 +/- 0.4 liters (D) for low and high Pdi, respectively. Thus, in trained subjects performing maneuvers aimed to distort the rib cage, no pressure difference was observed between the occluded and the nonoccluded lung during panting against the closed shutter. We conclude that it is unlikely that the mechanism proposed by Brown et al. might explain errors in lung volume measurements by body plethysmography in humans.
A 41-yr-old psychologically disturbed woman presented with attacks of paroxystic dyspnea, laborious expiration, cough, and expiratory wheezing. She had been treated for bronchial asthma and had developed an iatrogenic Cushing's syndrome. Wheezing had maximal intensity over the larynx, and fiberoptic bronchoscopy showed an almost closed glottis orifice during its production. Lung function tests were normal both before and during the attacks. Inhalation challenge tests with acetylcholine and histamine were negative. During the attacks the patient breathed near residual volume, and tidal flows reached the maximal flow-volume envelope. We suggest that wheezing was produced by high flows passing through a narrow glottis orifice. The association of expiratory wheezing of laryngeal origin with normal overall lung function should be kept in mind, because it can be easily confounded with bronchial asthma, and result in therapeutic errors.