Preliminary results of fast neutron teletherapy of metastatic cervical adenopathy

Between September 21, 1973 and May 9, 1975, 36 patients with metastatic cervical adenopathy from cancers primarily arising in the pharynx or oral cavity, including six with bilateral cervical involvement, received fast neutron teletherapy at the University of Washington. At the conclusion of treatment, the masses were no longer palpable in nine of 42 (21%) heminecks and were reduced more than 50% in 23 (55%). In 12 patients with partial regression, the masses eventually disappeared, so that in all, 21 heminecks (50%) or 20 patients (56%) were controlled for periods up to 66 weeks. Fixed cervical masses were controlled in 11 of 23 (48%) patients. These results, which must be sustained for longer observation periods, are comparable to results reported in the literature. Treatment was well tolerated; therefore, doses can be raised to study the influence on tumor control.     

Aggressive therapy does not substantially alter the long-term course of rheumatoid arthritis. So what else is new?

A consensus has evolved that there is little evidence supporting the view that the second line agents significantly alter long-term outcomes in rheumatoid arthritis. Consequently, changes in approaches to treatment currently being employed include earlier use of existing second line agents, their use in combinations, and greater use of corticosteroids. Our awareness that our current drugs, at best, fall considerably short of attaining the therapeutic results we would like to achieve causes us to look forward to the development of rationally derived biologic agents with considerable anticipation.     

Consultation-liaison psychiatry: a psychosomatic service in the general hospital

Consultation psychiatry, an outgrowth of the tenets of psychosomatic medicine that followed the departure from mental-hospital psychiatry to the general-hospital-based psychiatric units, is similar to those consultation services in other specialties available on medical-surgical wards. Its primary aim is to interpret the psychosocial phenomena of health and illness and to redirect the physician from disease- to patient-orientation and to a comprehensive approach. Its functions are diagnostic-therapeutic, instructional and research directed. The psychosomatic orientation is a sine qua non in the understanding of the psychosocial meaning of physical illness, its effect on psychic disability, the psychosocial adjustment of the patient and his family and his ability to adapt to illness and the hospital. An essential feature is the evaluation of the doctor-patient relationship, especially when severe illness requires serious interventions, including the consultation and its reciprocal effect upon the doctor-patient relationship. Liaison activity consists of interpretive-therapeutic mediation between the patient and the therapeutic team when strain endangers their satisfactory cooperation. The therapeutic activity must be short-term and so construed as not to interfere with the primary treatment. The instructional aspect is for the sake of the usual recipients of the service, as well as residents and students. Teaching the interview techniques, especially to students, should demonstrate the holistic approach, comprehensive diagnosis and the need of avoiding orthodox one-sidedness. This paper reviews briefly the scope and role of consultation psychiatry, compares its North American model with its status elsewhere and explores the resistances to it.     

Pigmented lesions in newborn infants

1058 newborn infants were examined. Forty-one (3-9%) had clinically discernible pigmented lesions compatible with melanocytic naevi. Biopsy was performed on thirty-four of the forty-one and of these; eleven, representing 1-01% of the infants, proved to be melanocytic naevi. No giant (garment) naevi were seen in this series. Two of the eleven naevi pathologically examined showed histological changes similar to those that have been reported in some giant naevi, but the remaining nine were not only different from criteria usually assigned to giant naevi, but they also differed from the usual adult naevi, in that most were predominantly junctional. None of the melanocytic naevi in this series showed any suggestion of malignant change. In newborn infants it is often impossible clinically to distinguish naevi from other types of pigmented lesions, as only eleven out of the thirty-four pigmented lesions were melanocytic naevi. Seven of the eleven melanocytic naevi were under 1-5 cm in diameter. No pigmented lesions were found on the palms, soles or genitalia.     

Continuous in-vivo blood-gas determination in man: reliability and safety of a new device

The Sentorr is a gas chromatograph that monitors Pa2 and PaCO2 every 4 min from a probe placed through an intraarterial cannula. The accuracy of this device and complications resulting from its use were studied in 46 patients undergoing cardiac surgical procedures with oxygen to nitrous oxide-halothane anesthesia. Sentorr blood-gas values were compared with simultaneous samples analyzed with standard electrodes. During relatively steady states of respiration and circulation, and in the lower (50-125 torr) range of oxygen tensions, the measurements correlated closely (r = 0.92). The device also functioned well during low-flow states, but during hypothermic cardiopulmonary bypass, the correlation was only fair (r = 0.62). When nitrous oxide was present in the inspired gas, Sentorr PaO2 readings were a third lower than actual PO2 measurements, an effect corroborated by an in-vitro experiment. Directional changes of oxygen and carbon dioxide tensions were always correct in all situations. Placement of the probe in a radial artery was unsatisfactory because it significantly interfered with blood pressure measurement and resulted in inaccurate results for this patient population. The brachial artery was a satisfactory site for insertion, although attenuation of the arterial pressure tracing by the presence of a Sentorr probe resulted in systolic pressure readings that averaged 12 torr lower with mean arterial pressure readings 5 torr lower. No increase in morbidity due to use of a Sentorr probe for brachial arterial pressure monitoring could be identified. The most potentially serious complication encountered was transient loss of a palpable pulse without interruption of blood flow in one or more distal arteries after decannulation. This was observed in seven patients (four of whom had diminished distal pulses whith normal flow before cannulation).     

Interaction between neuronal nitric oxide synthase and inhibitory G protein activity in heart rate regulation in conscious mice

Nitric oxide (NO) synthesized within mammalian sinoatrial cells has been shown to participate in cholinergic control of heart rate (HR). However, it is not known whether NO synthesized within neurons plays a role in HR regulation. HR dynamics were measured in 24 wild-type (WT) mice and 24 mice in which the gene for neuronal NO synthase (nNOS) was absent (nNOS-/- mice). Mean HR and HR variability were compared in subsets of these animals at baseline, after parasympathetic blockade with atropine (0.5 mg/kg i.p.), after beta-adrenergic blockade with propranolol (1 mg/kg i.p.), and after combined autonomic blockade. Other animals underwent pressor challenge with phenylephrine (3 mg/kg i.p.) after beta-adrenergic blockade to test for a baroreflex-mediated cardioinhibitory response. The latter experiments were then repeated after inactivation of inhibitory G proteins with pertussis toxin (PTX) (30 microgram/kg i.p.). At baseline, nNOS-/- mice had higher mean HR (711+/-8 vs. 650+/-8 bpm, P = 0.0004) and lower HR variance (424+/-70 vs. 1,112+/-174 bpm2, P = 0.001) compared with WT mice. In nNOS-/- mice, atropine administration led to a much smaller change in mean HR (-2+/-9 vs. 49+/-5 bpm, P = 0.0008) and in HR variance (64+/-24 vs. -903+/-295 bpm2, P = 0.02) than in WT mice. In contrast, propranolol administration and combined autonomic blockade led to similar changes in mean HR between the two groups. After beta-adrenergic blockade, phenylephrine injection elicited a fall in mean HR and rise in HR variance in WT mice that was partially attenuated after treatment with PTX. The response to pressor challenge in nNOS-/- mice before PTX administration was similar to that in WT mice. However, PTX-treated nNOS-/- mice had a dramatically attenuated response to phenylephrine. These findings suggest that the absence of nNOS activity leads to reduced baseline parasympathetic tone, but does not prevent baroreflex-mediated cardioinhibition unless inhibitory G proteins are also inactivated. Thus, neuronally derived NO and cardiac inhibitory G protein activity serve as parallel pathways to mediate autonomic slowing of heart rate in the mouse.     

Repeated measurement of respiratory function and bronchoconstriction in unanesthetized mice

A noninvasive forced oscillation technique was used to determine respiratory function in unanesthetized and spontaneously breathing mice. Pseudorandom noise pressure variations in a frequency range of 16-208 Hz were applied to the body surface, and the flow response was measured at the nose. From the pressure-flow relationship, respiratory transfer impedance was calculated. Study of intra-animal variability on a short- and a long-term basis revealed that the real part of respiratory transfer impedance was reproducible within 9%. The imaginary part appeared less reproducible (within 22%). Furthermore, bronchoconstrictive responses were investigated and analyzed by evaluation of respiratory resistance as measured at 16 Hz (Rrs16). During the first 15 min after ovalbumin challenge in ovalbumin-sensitized mice, Rrs16 was significantly increased [49 +/- 7% (SE)]. Inhalation of methacholine in untreated mice induced an increase in Rrs16 of 75 +/- 16% (SE). In saline-challenged animals, no significant changes were observed. This method enables evaluation of long-term respiratory function in mice and appeared to be a sensitive measure for bronchoconstriction.     

Inflammatory polyarthritis in the community is not a benign disease: predicting functional disability one year after presentation

OBJECTIVE: To predict which patients with early inflammatory polyarthritis presenting to primary care will be functionally disabled one year after presentation, in order to inform treatment and referral decisions. METHODS: The study population consisted of 381 patients notified to the Norfolk Arthritis Register, a primary care based inception cohort of patients with inflammatory polyarthritis. Patients were regarded as functionally disabled if they had a Health Assessment Questionnaire (HAQ) score of one or more. Clinical, laboratory, and demographic variables easily measured at baseline were analyzed for their ability to predict future disability. Recursive partitioning was used to create a simple decision tree to predict those patients who would be disabled at one year. A logistic regression model was generated on a sample of 277 patients and tested on an independent sample of 104 patients. This was compared with other models, one of which consisted of the 1987 ARA criteria. RESULTS: 112 (29%) patients had a HAQ score of at least 1 at one year. The strongest predictors of future disability were a high baseline HAQ, large joint involvement, female sex, and longer disease duration. The decision tree predicted disability accurately in 67% of patients. CONCLUSION: It is possible to predict functional outcome at one year among patients with early inflammatory polyarthritis presenting to primary care using simple clinical variables measured at baseline. Satisfying the 1987 ARA criteria could not be used to predict future disability.     

Forskolin stimulation of water and cation permeability in aquaporin 1 water channels

Aquaporin 1, a six-transmembrane domain protein, is a water channel present in many fluid-secreting and -absorbing cells. In Xenopus oocytes injected with aquaporin 1 complementary RNA, the application of forskolin or cyclic 8-bromo- adenosine 3',5'-monophosphate increased membrane permeability to water and triggered a cationic conductance. The cationic conductance was also induced by direct injection of protein kinase A (PKA) catalytic subunit, reduced by the kinase inhibitor H7, and blocked by HgCl2, an inhibitor of aquaporin 1. The cationic permeability of the aquaporin 1 channel is activated by a cyclic adenosine monophosphate-dependent mechanism that may involve direct or indirect phosphorylation by PKA.     

Review of the nutrition policy of the Arnhem Land Progress Association

In this experiment, the effect of trehalose on the preservation of rat gracilis muscle flaps was studied. The muscle flaps were preserved in 4 degrees C Euro-Collins solution or 4 degrees C trehalose-Euro-Collins solution for 6, 12, 24, 48, 72, and 96 hours, and then replanted in the same rats using microsurgical techniques. Immediately after preservation and 1 week after replantation, the levels of adenosine triphosphate and creatine phosphate in flaps preserved in the trehalose-Euro-Collins solution were significantly higher than those in flaps preserved in the Euro-Collins solution. In the 4 degrees C Euro-Collins solution group 1 week after replantation, focal necrosis, hyaline degeneration, and proliferation of fibroblasts were seen after 12 hours of preservation, and, after 48 hours of preservation, there were no surviving flaps. In the 4 degrees C trehalose-Euro-Collins group, focal necrosis, hyaline degeneration, and proliferation of fibroblasts were seen only after 24 hours of preservation, and, after 96 hours of preservation, two of eight flaps survived. These findings indicate that trehalose was effective in the preservation of muscle flaps.