Tri-state region pulmonary rehabilitation survey. Delivery of exercise conditioning services. The Pulmonary Rehabilitation Committee, Tri-State Society for Cardiovascular and Pulmonary Rehabilitation.

PURPOSE: This report analyzes the delivery of exercise conditioning services in the 1991 Pennsylvania, New Jersey, and Delaware regional survey of pulmonary rehabilitation programs. METHODS: Data from a questionnaire was analyzed with special consideration given to whether the program provided services for patients with only pulmonary diseases (n = 41) or with cardiac and pulmonary diseases (n = 18). RESULTS: All 59 programs included exercise conditioning. Most programs (67%) used oxygen saturation and/or expired gas analysis for writing exercise prescriptions. Only pulmonary programs used 6- or 12-minute walk data. The exercise prescription was written by nonphysicians in 51% of the programs. Most pulmonary-only programs used respiratory therapists by themselves or in combination with other professionals as exercise supervisors (71%). Cardiopulmonary programs used exercise physiologists by themselves (22%) or nurses by themselves or in combination with other professionals (50%). For all programs, the standard for ratio of patients to exercise staff averaged 3.0:1. Pulmonary-only programs did slightly but significantly more continuous arterial oxygen percent saturation (SaO2) monitoring rather than spot checking. A standard determining the use of supplemental oxygen during exercise was reported by 78% of all programs. Most used supplemental oxygen after observing the SaO2 level falling to < 90%. Electrocardiograph monitoring was done in 66% of pulmonary-only programs, but in 94% of the cardiopulmonary programs. Maintenance sessions were offered by 64% of the pulmonary-only programs and also by 78% of the cardiopulmonary programs. CONCLUSION: The type of rehabilitation program, either pulmonary-only or cardiopulmonary, appears to influence the exercise conditioning services used by the pulmonary patient.

Tri-State Regional Pulmonary Rehabilitation Survey. Program characteristics and practices.

PURPOSE: This report summarizes the pulmonary rehabilitation characteristics found in the 1991 survey of programs in the Pennsylvania, New Jersey, and Delaware region. METHODS: A listing of 111 potential Tri-state regional programs with pulmonary rehabilitation was compiled. A 34-item questionnaire was developed. Using multiple mailings and phone-call follow-up, 59 programs of 100 the active programs in the region returned the questionnaires. Programs that were providing services to patients with pulmonary disease were compared to those focusing on patients with cardiac and/or pulmonary disease. RESULTS: A third of all programs (31%) used combined cardiopulmonary services. Pulmonary-only programs averaged 1.7 hours per day, and cardiopulmonary programs averaged 1.1 hours per day (P < .01). Both types of programs averaged 2.4 days per week. Average duration of pulmonary-only programs was 8.7 weeks, and duration of cardiopulmonary programs was 10.6 weeks (P < .05). Most programs (85%) required referral from the patients' primary physician. Many programs (64%) reported that local physicians other than the program's medical director referred a majority of the patients. Almost all programs (92%) performed exercise testing before initiating pulmonary rehabilitation. Post-rehabilitation discharge planning seemed to be based in many programs on performance measures taken during the final rehabilitation sessions or from a final 6- or 12-minute walk. Educational sessions were provided by 95% of the programs. Maintenance sessions were not offered by 39% of the programs. Seventy-three percent of the pulmonary-only programs and 44% of the cardiopulmonary programs offered support groups (P < .05). The pulmonary-only program coordinator's specialty was mostly respiratory therapy (70%), whereas in cardiopulmonary programs, coordinators tended to be nurses (39%) or from other nonrespiratory specialties (28%). No respiratory staff were used by 38% of the cardiopulmonary programs. CONCLUSIONS: The type of rehabilitation program, either pulmonary-only or cardiopulmonary, appears to influence many program characteristics (e.g., hours per day, weeks in duration, coordinator's specialty, and staffing).

WY 18,251 (Tilomisole), an analog of levamisole: tolerability, and immune modulating effects in cancer patients.

Wy 18,251 (Tilomisole; Wyeth Laboratories, Philadelphia, PA, USA) is a benzimidazole that is structurally similar to the antihelminth levamisole that has recently been approved for the adjuvant treatment of colon cancer. In preclinical models, Tilomisole caused less agranulocytosis than levamisole, but retained immunomodulating capabilities. We examined the effects of Tilomisole administered to cancer patients in four different dose schedules: 60 mg/m2 orally (p.o.) weekly, and 60, 300, or 960 mg/m2 p.o. daily for 1 month. All patients were immunosuppressed when treatment was initiated as defined by standardized assays of phytohemagglutinin, concanavalin A, pokeweed mitogen, and mixed lymphocyte responses. Tilomisole was well tolerated with no significant side effects in 25 patients. There were no antitumor responses noted in this setting of metastatic cancer. There was no improvement in concanavalin A or pokeweed mitogen assays at any dose or schedule, but there was sustained improvement in mixed lymphocyte reaction and phytohemagglutinin assays at the 60 mg/m2 daily dose. This drug may have favorable biological response modifying effects in vivo and be a suitable alternative to levamisole in cancer treatment, especially if agranulocytosis is a significant problem associated with widespread use of levamisole.

Morphology and electrical properties of Schwann cells around the giant axon of the squids Loligo forbesi and Loligo vulgaris.

The first successful dye-fills of Schwann cells around the split giant axon of Loligo show them to be spindle-shaped cells ca. 600 microns long and 20 microns wide lying parallel to the axonal axis. There are some 50,000 Schwann cells per cm2 of axonal membrane. Only a small part (ca. 6% of each Schwann cell membrane) is in contact with the periaxonal space, the remainder is overlain by adjacent Schwann cells, or applied to the basal lamina. The mean membrane potential of the Schwann cells in artificial seawater (ASW) varies from around -40 mV in fresh split-axon preparations to around -60 to -70 mV after 1-2 h; this hyperpolarization is not seen in preparations dissected and maintained in Ca2(+)-free ASW. Electrical- and dye-coupling (abolished by prior octanol treatment) is present between Schwann cells, but is weaker in cells with lower (less negative) membrane potentials. The implications for potassium homeostasis around the axon are briefly discussed.

Recent outcomes for patients with carcinoma of the lung.

We undertook a retrospective study of all lung cancer patients diagnosed between 1978 to 1982 and seen at the University of California San Diego affiliated hospitals. There were 390 evaluable patients; the vast majority were men. Overall median survival was 8 months and was similar for all histologic types. Completely asymptomatic patients had a median survival of 20.1 months while symptomatic patients had a median survival of 5-8 months. Retrospective application of the new clinical staging system for lung cancer increased the survival distinction between clinical Stage I and Stage II disease. Median survival for small cell carcinoma of the lung was 10 months: 16.6 months for disease limited to the chest, and 5.8 months for metastatic disease. Median survival for Stage III nonsmall cell lung cancer patients was only 5 months. Only those asymptomatic patients with small lesions which were detected incidentally or by screening chest x-ray had any likelihood of long-term, disease-free survival with more than 60% alive two years after diagnosis. This study suggests that screening and early detection programs in existence during the period of observation were not effective in detecting early disease, and that no therapy of advanced diseases [Stages II through IV] was sufficiently efficacious to be considered standard.

Cooling rate and ice-crystal measurement in biological specimens plunged into liquid ethane, propane, and Freon 22.

Specimens sandwiched between copper planchettes were plunged up to a depth of 430 mm into coolants used for cryofixation. Hydrated gelatin containing a miniature thermocouple was used to mimic the behaviour of tissue during freezing. Gelatin and red blood cells were used for ice-crystal analysis. Ethane produced the fastest cooling rates and the smallest ice-crystal profiles, and Freon 22 produced the slowest cooling rates and the largest crystal profiles. Smaller crystal profiles were often seen in the centre of the specimens than in subsurface zones. The results show that ethane, rather than propane, should be used for freezing metal-sandwiched freeze-fracture specimens by the plunging method, and probably also in the jet-cooling method. They further suggest that good cryofixation could occur at the centre of thin specimens rather than only at their surfaces. Comparison between theoretical and experimental ice-crystal sizes was satisfactory, indicating that where the experimental parameters can be defined then realistic predictions can be made regarding cryofixation results.

Breast cancer imaging with In-111 human IgM monoclonal antibodies: preliminary studies.

Detection of specific tumor sites was studied with scintigraphy and radiolabeled human IgM monoclonal antibodies (MoAbs). Ten patients with metastatic breast cancer received an infusion of one of three indium-111-labeled anti-breast carcinoma MoAbs. The time of infusion ranged from 30 minutes to 2 hours. Three patients received YBB-190 at total doses of 2, 4.25, or 11 mg, four patients received YBM-209 at total doses of 1 mg (n = 1) or 20 mg (n = 3), and three patients each received 22 mg of YBY-088. Imaging was performed immediately after infusion and at 4, 24, 48, 72, 120, and 144 hours. Many presumed sites of metastatic disease were imaged in three of the four patients who received 20 mg of YBM-209 and in two of the three patients who received YBY-088. Tumor was not detected in any of the patients who received YBB-190, in the patient who received a 1-mg dose of YBM-209, or in the patient who received YBY-088 and in whom a biopsy of tumor tissue failed to demonstrate target antigen. The authors conclude that In-111-labeled human IgM MoAbs can target human breast cancer, but antigen expression and antibody dose determine successful immunoscintigraphy.

Safety considerations regarding the use of propane and other liquefied gases as coolants for rapid freezing purposes.

Liquid propane and similar coolants are used in the rapid freezing of biological specimens. These coolants form explosive gas mixtures with air, with a 14,000-fold increase in volume over that of the liquid. The liquefied gases have high vapour pressures and, unless they are maintained below their flashpoint, the vapour above them will reach ignitable concentrations. The flashpoint of liquid propane is -104 degrees C. Ethane has a higher vapour pressure, and vapour mixed with air above liquid ethane can be ignited at a coolant temperature of -130 degrees C. The danger is minimized if the coolant is maintained near its freezing point and under a nitrogen atmosphere, in a fume cupboard. Liquid nitrogen evaporates to a 690-fold increase in volume at room temperature. It is important to ventilate the working area, especially when cryo-sectioning in a small room, otherwise there is a possibility of asphyxiation.

Radioimmunodetection of cancer with the use of indium-111-labeled monoclonal antibodies.

We have infused 13 111In-labeled murine IgG monoclonal antibodies (MAb) into 73 patients who had been diagnosed as having 7 types of cancers, and 3 111In-labeled human MAb into 8 patients with breast cancer. To each patient, 1.5-5 mCi attached to a maximum of 1 mg MAb had been given in a total MAb dose of 0.5-500 mg. The most encouraging overall results have been obtained with anti-human T-cell MAb T101 (33 of 33 tumor sites imaged in 5 patients), antimelanoma MAb P96.5 (47 of 88 sites imaged in 21 patients), anti-prostate MAb PSA399 (14 of 21 sites imaged in 4 patients), and anti-colon MAb ZCE025 (16 of 26 sites imaged in 12 patients). Poor imaging results were related to lower doses, reactivity with circulating cells, and limited antigen expression in various tumor sites. The problems involved in radioimmunodetection included low extraction of MAb from the serum by the tumor that resulted in poor tumor uptake of the radiopharmaceutical, and high background activity in the liver, heart, spleen, and gastrointestinal tract that made imaging difficult in those areas. Heterogeneous antigen production leaves some tumor deposits without targets, and the immunogenicity of the MAb limits use of these agents repetitively in humans. Nevertheless, these early results are encouraging for their potential diagnostic and therapeutic applications.

The relative efficiency of cryogens used for plunge-cooling biological specimens.

Coolants used for freezing biological specimens were tested for cooling performance in the continuous plunge mode. Results from bare thermocouples showed that ethane cooled faster than propane or a propane:pentane mixture, even when warmed to 25 K above its freezing point. Propane coolants were more efficient than Freon 22 and the slowest cooling occurred in boiling liquid nitrogen. Hydrated gelatin specimens showed similar results with ethane cooling about 33% faster than propane. Epoxy resin specimens cooled faster than hydrated gelatin specimens of similar size. Hydrated and resin specimens cooled over increasing distances as plunge velocity increased. A bare thermocouple, however, cooled over a constant distance when plunged above a critical velocity. This phenomenon may reflect vapour formation and its suppression at high plunge velocities. The rate of cooling in hydrated specimens is shown to have an absolute limit and cannot be modelled by bare thermocouples or resin specimens.

Continuous infusion of T101 monoclonal antibody in chronic lymphocytic leukemia and cutaneous T-cell lymphoma.

We report results of 24-h continuous infusions of murine monoclonal antibody T101 in six patients with chronic lymphocytic leukemia (CLL), and 10 with cutaneous T-cell lymphoma (CTCL), at doses of 10, 50, 100, or 500 mg. Similar side-effects were seen in CLL and CTCL, including direct toxic effects of therapy, such as fever, sweats, and chilling, and a 30% frequency of allergic manifestations. In vivo binding of T101 to target cells in blood, skin, lymph nodes, tumor masses, and bone marrow was demonstrated. Antigenic modulation occurred rapidly in all cases, and persisted throughout the infusion period. Peak serum T101 levels for equivalent doses were somewhat higher, and persisted longer in CTCL, perhaps because of differences in the number of circulating target cells. Antimouse antibodies were demonstrated in 5 of 10 CTCL vs. 0 of 6 CLL patients. In all five cases, there was a substantial component of T101 specificity in the antimouse response. Brief objective clinical responses were observed in 4 of 10 CTCL and 2 of 6 CLL patients. Acute anti-tumor effects of T101 were substantially more dramatic in CTCL than CLL, but appeared limited by antigenic modulation and the emergence of antimouse antibodies. In view of the in vivo binding and modulation, more durable anti-tumor effects may be achievable with cytotoxic immunoconjugates of this monoclonal antibody.

Contractile properties and ultrastructure of three types of muscle fibre in the dogfish myotome.

Three main types of fibre can be differentiated in the adult dogfish myotome at the immediate post-anal level. An outer band of muscle consists of 80-90 pale multiply innervated fibres (superficial fibres). These fibres are 80-90 micron in diameter, lack M-lines and have a low Ca2+-activated myosin ATPase activity. Volume densities of myofibrils (Vv(my,f] and mitochondria (Vv(mt,f] are respectively 76 and 9.5%. Beneath this layer are around 8000 red multiply innervated fibres. These have an average diameter of 25-40 micron. Vv(my,f) and Vv(mt,f) are 62 and 21% respectively, and M-lines are present. Around 11 000 white focally innervated twitch fibres lie beneath the red fibre zone. White fibres with an average diameter of 80-120 micron have a high Ca2+-activated myosin ATPase activity and Vv(my,f) and Vv(mt,f) are 78 and 5% respectively. Contractile properties of single skinned fibres were determined at 12 degrees C. Maximum Ca2+ activated tensions (kN m-2) and unloaded contraction speeds (muscle lengths s-1) were 49 and 0.5 for superficial, 70 and 1.4 for red and 180 and 4.4 for white muscle fibres. Superficial fibres have not been reported in other elasmobranchs with the exception of the closely related nursehound (Scyliorhinus stellaris L.) It is suggested that they are specialized for sustained force generation, having a tonic (postural) rather than a locomotor role.

Plunge-cooling of tissue blocks: determinants of cooling rates.

Tissue blocks have been plunged into a liquid coolant and the resultant ice-crystal damage is discussed. Some blocks have been frozen without apparent ice-crystal damage; they were not treated with cryo-protectants but were mounted on streamlined foil supports which separated the specimen from the thermal mass of the support pin. Hydrated gelatin specimens of various sizes have been built around thermocouples and plunged at different speeds. Results show that cooling is relatively slow in specimens mounted on solid metal supports. In specimens mounted on foil supports cooling is related to plunge velocity in 0.25 mm diameter specimens but in 1 mm diameter specimens cooling occurs mainly after coming to rest. In 0.5 mm diameter specimens cooling is related to plunge velocity at low immersion speeds but then it decreases with increasing plunge velocity; this trend should allow monitoring of attempts to improve the efficiency of the plunge-cooling technique.

Magnesium chloride as an anaesthetic for cephalopods.

Magnesium chloride is an effective anaesthetic and narcotizing agent for cephalopod molluscs. Individuals belonging to five genera (decapod and octopod) were anaesthetized and subsequently revived at temperatures ranging from 13 to 22 degrees C. At no stage of anaesthesia does MgCl2 appear to cause any trauma. There is evidence that MgCl2 acts centrally on the nervous system to induce anaesthesia. This salt, cheap, readily available and convenient to use, is recommended over urethane or ethanol as a suitable anaesthetic or narcotic for use with cephalopods.

Comparison of isogravimetric and venous occlusion capillary pressures in isolated dog lungs.

Venous occlusion capillary pressures (Pcv) were simultaneously compared with isogravimetric capillary pressures (PcI) in the same isolated perfused dog lung preparations. For 26 determinations, PcI averaged 1.23 +/- 0.22 (SE) mmHg higher than Pcv. However, the two measurements of capillary pressure were highly correlated (r = 0.99), and the following regression equation was obtained: Pcv = 1.12 PcI - 2.1. Pcv could be easily measured several times in the same preparation, either by total venous occlusion or regional venous occlusion using a Swan-Ganz balloon catheter. In addition, Pcv did not require an isogravimetric state for its determination. These data suggest that the major sites of filtration and vascular capacitance in the pulmonary circulation reside in the microvessels and that the more easily determined Pcv is an adequate measure of the average capillary filtration pressure in the lungs.

Microangiopathic hemolytic anemia, thrombocytopenia, and renal failure in patients treated for adenocarcinoma.

Microangiopathic hemolytic anemia and thrombocytopenia secondary to disseminated intravascular coagulation is a well-described complication of widely metastatic carcinoma. The authors report four cases of gastric carcinoma, one case of colon cancer, and one case of adenocarcinoma of unknown primary in which the patient developed a syndrome analogous to thrombotic thrombocytopenic purpura, consisting of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure without definite evidence of disseminated intravascular coagulation. In contrast to previous reports, postmortem examination in three of the cases revealed no recurrence or only microscopic foci of residual tumor. In the remaining three, there was clinical and pathologic evidence of grossly disseminated carcinoma. Also in contrast to previous cases, all patients evidenced azotemia and proteinuria at the onset of the syndrome and ultimately uremia was a contributing cause of death. Coagulation profiles showed prolonged thrombin times and elevated fibrin degradation products in four instances and did not distinguish the patients with grossly metastatic disease from those with no tumor or only microscopic residua. Circulating immune complexes containing carcinoembryonic antigen were found in the patient with metastatic colon carcinoma. The syndrome was clinically identical whether or not grossly metastatic tumor was present, and it should not be attributed to advanced disease without definite clinical or pathologic evidence of a recurrence.