Susceptibility and resistance to environmental carcinogens in the development of carcinoma of the lung

Eight selected cases are presented to show different effects of the environment on the lung. Some appear to lack resistance to environmental carcinogens. The variations in response and an assessment of the carcinogens involved are discussed. Further study of these poorly understood etiologic factors is needed.     

The inappropriate use of acute hospital beds in an inner London District Health Authority

The requirement for District Health Authorities to assess the health care needs of their population implies that they must consider how well acute hospital care meets these identified needs. This study, which was conducted in an inner London health district, identified that 123 (14.6%) patients were perceived by medical and/or nursing staff to be inappropriately located in an acute bed. This group was dominated by patients aged 65 years or above, those in general and geriatric medicine, those with a length of stay of 30 days or more, and those with high levels of physical and mental dependency. The main reasons for patients being labelled as 'inappropriate' were the need for non-acute health services (eg rehabilitation, terminal care etc), a need for nursing home places or because of social or housing problems. Five months after identification, the notes of 100 of the 123 inappropriate patients were traced. Retrospective classification of these notes using the more 'objective' Oxford Bed Study Instrument showed that 97 patients were still defined as inappropriate. Details of the length of inappropriate stay were available for 74 patients who accrued 7,519 inappropriate bed days at a cost of 836,547 pounds. These patients are an illustration of the potential failings of current health and social care systems and highlight the need for imaginative care solutions which bridge this divide.     

Computerized photo-plethysmography of the finger

A microcomputer system for studying photo-plethysmography of the finger (PPF) was designed and applied to 50 non-premedicated healthy boys (one to ten years old) undergoing general anaesthesia (halothane in 70% N₂O, with mechanical ventilation) for outpatient inguinal hernia repair. The purpose of this study was to assess the accuracy of computerized estimations of the photo-plethysmographic (arterial waves) amplitude and to evaluate whether or not PPF allows discrimination between two different surgical stimuli (skin incision, and manipulation of the spermatic cord). When anaesthesia was stable for at least five minutes (end-tidal halothane=1.25–1.5%;PetCO₂=32–38 mmHg; SpO₂≥98%; rectal temperature=36.3–37°C; ambient operating room temperature=20–21°C), and immediately before the skin incision, computerized estimations of the photo-plethysmographic (arterial waves) amplitudes (PPA) were recorded and saved for later comparison with direct (manual) measurements of the plethysmographic tracing, using an arbitrary scale of 0–255 units. Also, the values of PPA, systolic blood pressure, and pulse rate recorded immediately before the skin incision were later compared with the maximum changes in these same values recorded 30–90 sec after skin incision, and 30–90 sec after manipulation (traction + dissection) of the spermatic cord. Six boys (three to ten years old) stayed quiet enough, during induction of anaesthesia by mask, to allow regression analysis of PPA, systolic blood pressure, and pulse rate (Y) on end-tidal halothane/70% N₂O (X). Computerized estimations tended to give a higher reading, by between 0.2 to 0.8 units, than direct measurements. Spearman and Kendall correlations showed that computerized and direct measurements were associated (P<0.0001), the Kolmogorov-Smirnov’s test revealed that the two distributions were identical (P=1), the mean difference between computerized and direct estimations of the PPA was 0.52±1.08 units, and the limits of agreement (?1.6 and 2.6 units) were small enough to be confident that computerized (automatic) estimations of PPA can be used for clinical purposes. Skin incision caused a smaller decrease of PPA (24%) than manipulation of the spermatic cord (37%). Changes in PPA were more pronounced than changes in systolic blood pressure or pulse rate (P<0.05). Linear regressions and Fisher’s exact test (two-tailed) showed that, during induction of anaesthesia with halothane in 70% N₂O by mask (n=6), changes in end-tidal halothane concentration were related more to changes in PPA than to changes in systolic blood pressure and/or in pulse rate (P<0.05). In conclusion, computerized PPF allows discrimination between two different surgical stimuli, provides quantification of the sympathetic response to preoperative anxiety, and may be useful for studying pre-anaesthetic sedation.     

Trends in presentation of congenital heart disease in a population-based study in Malta

Differing pathological haemodynamics in cardiac malformations lead to varying modes and timings of presentation. This study identifies historical trends in presentation of congenital heart disease in a population-based study. All patients diagnosed as having congenital heart disease in Malta between 1960–1994 were included (n = 868). Analysis was carried out on trends in referral sources, modes of presentation and birth prevalence. The number of patients diagnosed with congenital heart disease increased over the period under study. For both patients not requiring intervention (n = 283) and those requiring intervention (n=585), the proportion diagnosed prior to hospital discharge increased (p 0.005). There was a decreasing trend for general practitioners to refer cases (p < 0.0001), and an increasing trend for paediatricians to refer such patients (p 0.0003). The commonest presentation to the general practitioner was an incidental finding (92%), while paediatricians referred more patients for cyanosis or heart failure (p 0.005). For lesions not requiring intervention, the commonest lesion referred was ventricular septal defect from all sources. For lesions requiring intervention, the commonest lesion detected prior to hospital discharge was tetralogy of Fallot. Atrial septal defects were the commonest lesions detected after discharge by both paediatricians and general practitioners. An increase in the proportion of hospital diagnoses is attributed to increasing rate of hospital delivery, and greater training and experience in doctors performing neonatal examinations prior to discharge. Patients diagnosed after discharge are increasingly diagnosed by paediatricians due to an increasing pool of paediatricians and better parent awareness and education.     

Kawasaki disease in Malta

Kawasaki disease is an acute febrile illness of childhood of unknown origin which may cause coronary arteritis and death. The Maltese incidence of 3.2/100,000 population <5 years of age is similar to that reported in non-Asiatic communities. None of the patients had coronary arteritis or other complications. A significant decline in delay to diagnosis was found, attributed to increased awareness of the disease.     

Bilateral macular hemorrhage after laser in situ keratomileusis

· Background: This is the first report of a bilateral submacular hemorrhage after LASIK surgery in an extreme myo pic patient. A 31-year-old man underwent bilateral surgery for correction of –16.75+0.75×70° and –16.50+0.50×55°. · Methods: Case report. · Results: One day after surgery the patient’s uncorrected visual acuity was in the 20/50 range OU and by 17 days after surgery his visual acuity had declined to 20/200 range. Fundus examination showed multifocal subretinal macular and posterior pole hemorrhages. Fluorescein angiography showed some macular lesions compatible with lacquer cracks. · Conclusions: Preoperative and postoperative fundus examination is important to detect this phenomenon. Patients should be informed of this rare complication. Received: 2 June 1998 Revised version received: 16 November 1998 Accepted: 17 November 1998     

Correlations between experimental chemotherapy in the murine glioma and effectiveness of clinical therapy regimens

Summary Intracerebral murine glioma 26 was used as a model system for evaluating two-drug combinations of antitumor agents. BCNU was combined with either procarbazine, dianhydrogalactitol, or ellipticine. CCNU was combined with procarbazine. All combinations were more active than the individual drugs alone. The most potent combinations achieved 85–100% tumor cure at 120 days, with combined toxicity indices of 0.25 (CCNU-procarbazine) to 1.30 (BCNU-dianhydrogalactitol). The experimental data were compared to clinical studies with CCNU, procarbazine, and vincristine, and BCNU-procarbazine.American Cancer Society Faculty Research Award FRA-155This work was supported by NIH Center Grant CA-13525, and gifts from Phi Beta Psi Sorority and the Margaret M. Anton Memorial Fund Reprint requests should be addressed to:Editorial Office, 350 Parnassus Avenue, Suite 807, University of California, San Francisco, California, 94143, USA     

Heuristic modeling of drug delivery to malignant brain tumors

It is apparent that chemotherapy against malignant brain tumors is generally ineffective. While some agents are more effective than others, none appreciably alters the clinical course of and the poor prognosis for patients with brain tumors. Even though new and more effective agents are being or will be developed, chemotherapy depends as much on the delivery of drug as it does on the drug used. Therefore, we have defined factors that we believe are of primary importance in drug delivery to brain tumors, and, using computer simulation, we have modeled the effects of these factors. In this article we discuss (a) the extent of the breakdown in the blood-brain barrier (BBB) that accompanies the development of malignant tumors in the brain, (b) factors that influence drug transport from tumor capillaries to tumor cells at varying distances from the capillaries, (c) the problems inherent in drug delivery from a well-vascularized tumor outward to normal brain tissue that might harbor malignant cells but that does not have leaky vessels (i.e., normal BBB), and (d) the difficulties in drug delivery from a well-perfused, highly permeable outer tumor shell to a central, poorly perfused tumor core.This work was supported by American Cancer Society Grant CH-75 and NIH Program Project Grant CA-13525. V. A. L. is the recipient of an American Cancer Society Faculty Research Award (FRA-155).     

Phenotypic differences in survival to an experimental acute carbon monoxide intoxication

Male and female 45-day-old mice of two inbred (CBA and C57B1) and of one outbred (OF₁), SPF (specific pathogen free), strains, LD_12:12 (L = 150 lx) synchronized, were submitted to an acute carbon monoxide challenge giving an overall survival close to 50%. Under these conditions significantly (P < 0.001) less CBA survived than the two other strains. A sex-related significant (P < 0.001 difference was observed in OF₁. Strain survival differences are independent of body weights and of respiratory and displacement activity, but appear to be related to behavior reactions towards environmental stresses. These phenotypic differences are similar to previous findings obtained with these three strains of mice submitted to a 50% survival acute hypoxic hypoxia (M. Stupfel, A. Perramon, P. Merat, J. M. Faure, and H. Masse, 1979, Comp. Biochem. Physiol., 64A, 317–323).