Aortocoronary bypass surgery: Correlation of angiographic symptomatic and functional improvement at 1 year. Angiographic changes in the coronary circulation were evaluated in 60 patients 1 year after aortocoronary bypass surgery, and their relation to the postoperative clinical status was examined. Of 124 grafts implanted, 26 were closed, 7 stenotic and 91 (74 percent) patent at 1 year. Progression of occlusive disease occurred in 21 of 57 (37 percent) nongrafted and 78 of 123 (63 percent) grafted vessels. On the basis of location and severity of progression, significant lesions bypassed and patency of grafts, postoperative coronary perfusion was considered optimal in 16 patients (Group I), better in 24 (Group III). Complete freedom from chest pain or lessening of pain (improvement by two New York Heart Association functional classes) occurred in 88 and 79 percent of patients in Group III. Positive preoperative treadmill stress tests became negative after surgery in five of six patients in Group I, five of eight in Grojp II and three of eight in Group III. This study demonstrates that when progression of disease, graft patency and extent of revasculariztion are considered in combination, the postoperative angiographic status of the coronary circulation correlates well with clinical improvement at 1 year. These findings support the hypothesis that improved blood supply to ischemic myocardium is a major factor contributing to relief of angina pectoris after saphenous vein bypass surgery.


Chronic carriers of hepatitis B antigen (HBsAg). Histological, biochemical, and immunological findings in 31 voluntary blood donors. Among 289 HBsAg carriers detected by the Montreal Red Cross Blood Transfusion Service and seen by our group, 31 submitted voluntarily to liver biopsy. These 31 carriers have now been followed for 10-33 months (mean: 23) and all remained positive for HBsAg. 15 of these 31 subjects had lived in institutions during infancy or childhood and none were drug users. Histological examinations revealed 24 cases of chronic persistent hepatitis (CPH), 2 cases of chronic aggressive hepatitis, 2 with steatosis, and 3 with normal liver. On repeated determination, 16 of the 31 subjects had at least one elevated transaminase level. Transaminases levels could not be correlated with the histological diagnosis. 4 cases had positive antinuclear antibodies, all in the CPH group, a finding that could not be correlated with any clinical, biological, or histological findings. The search for other autoantibodies and the immunoglobulin determinations were totally unrewarding. Thus, it appears that chronic HBsAg carriers in Montreal voluntary blood donors often have chronic hepatitis, usually persistent, occasionally aggressive; liver biopsy still remains the most useful approach in the evaluation of these HBsAg carriers. The HBsAg-carrier state seems to be well tolerated, but further long-term studies are needed to understand the natural history of this condition.


Autoimmune factors in African cirrhosis. Correlation with hepatitis B surface antigen and antibody. Sera were tested for autoantibodies in 98 patients with cryptogenic cirrhosis in Uganda and results correlated with serological tests for hepatitis B surface antigen (HBs Ag) and antibody to HBs Ag (HBs Ab). Smooth muscle antibodies (SMA) were detected in 23 (24%) of the patients but there was no difference in the incidence of SMA between HBs Ag-positive and negative cases. Antinuclear antibodies (ANA) were detected in five cases; mitochondrial, gastric and thyroid antibodies were not found in any patient. Unlike other geographical locations autoimmune mechanisms appear to play little part in the progression of chronic liver disease in Uganda Africans. Hepatitis B surface antigen was present in 36 (37%) and HBs Ab in 47 (48%) of the patients. Although evidence for past exposure to hepatitis B virus (as shown by detection of HBs Ab) was present in at least 30 out of the 62 HBs Ag-negative cases, there was no greater incidence of autoantibodies in HBs Ag-negative patients with or without HBs Ab. Persistent infection with hepatitis B virus and continuing liver damage may be an important factor but these results do not favor a role for the virus in causing chronic liver disease by triggering off an autoimmune reaction.


Relief of angina pectoris in patients with occluded coronary bypass grafts. Thirty-two patients from a larger series of subjects undergoing routine postoperative evaluation of the aortocoronary saphenous bypass graft procedure were found to have one (20 patients) or all (12 patients) of the implanted grafts totally occluded. Such occlusion occurred in association with persistent postoperative subjective improvement manifested by a significant diminution or complete disappearance of angina pectoris. Postoperative myocardial infarction was documented in only seven cases, and the possibility of successful partial revascularization could be logically applied to only 20 of these 32 patients. Other suggested mechanisms for relief of angina pectoris in this setting are mentioned, although none is scientifically proved. It is concluded that (1) the marked subjective improvement documented in this population does not universally correlate with anatomic success and that (2) a diminution in the degree of angina pectoris cannot be clinically applied as a reliable indicator of postoperative graft patency.


Diagnosis of von Willebrand's disease. A comparative study of diagnostic tests on nine families with von Willebrand's disease and its differential diagnosis from hemophilia and thrombocytopathy. Nine probands with von Willebrand's disease, and their family members, totalling 43 people, were examined. Twenty-seven had a history of bleeding; 29 had an increased factor VIII activity:factor VIII related antigen ratio; 24 had a decreased factor VIII related antigen; 23 had a prolonged bleeding time; 19 had a reduced platelet adhesiveness; 16 had a decreased factor VIII activity; and 14 had an abnormal ristocetin-induced platelet aggregation. Eight members with both normal beleeding time and normal factor VIII activity were found to have other abnormal tests: elevated ratio of factor VIII activity to factor VIII related antigen in seven; decreased factor VIII related antigen in four; and reduced platelet adhesiveness in one. Therefore, ratio of factor VIII activity to factor VIII related antigen and factor VIII related antigen are more sensitive and may be used for the detection of heterozygous carriers of von Willebrand's disease. Although patients with thrombocytopathy may have a prolonged bleeding time, decreased platelet adhesiveness and reduced platelet aggregation by ristocetin, their factor VIII activity, factor VIII related antigen and ratio of factor VIII activity to factor VIII related antigen are normal and their abnormal ristocetin test cannot be corrected by the addition of factor VIII concentrate. Hemophilic subjects and hemophilic carriers, who are deficient in factor VIII activity, usually have a normal bleeding time, normal platelet adhesiveness, and normal ristocetin test. In contrast to patients with von Willebrand's disease, their factor VIII related antigen is normal or slightly increased and their ratio of factor VIII activity to factor VIII related antigen is significantly reduced. We conclude that ratio of factor VIII activity to factor VIII related antigen and factor VIII related antigen are not only more sensitive but also more specific for the diagnosis of von Willebrand's disease.


Failure of AHF concentration to control bleeding in von Willebrand's disease. A newly available dried concentrate of antihemophilic factor (Profilate, Abbott Laboratories) was compared with standard, blood-bank prepared cryoprecipitate in the control of bleeding in a patient with von Willebrand's disease. Profilate effectively raised plasma levels of factor VIII but produced only half the expected increase in plasma ristocetin aggregation factor (RAF), and this RAF did not bind readily to the platelets in the presence of ristocetin. Furthermore, the Profilate had little effect upon the bleeding time or the clinical hemorrhage. In contrast, the cryoprecipitate did increase plasma RAF to the expected level, and this RAF bound readily to the patient's platelets in the presence of ristocetin. Cryoprecipitate promptly controlled bleeding. We conclude that the RAF present in Profilate retains in vitro activity but is incapable of augmenting platelet function in vivo.


Effects of chlorobutanol and bradykinin on myocardial excitation. The negative inotropic effect of a commonly used formulation of bradykinin (Sandoz BRS-640) was found to be due to chlorobutanol, a constituent of the preparation. Solutions containing up to 100 mug of crystalline bradykinin/ml had no effect on tension or action-potential shape. Chlorobutanol (500 mug/ml) caused a 30% decrease in contraction amplitude and a 20% increase in action-potential duration. Chlorobutanol lowered conduction velocity and induced conduction failure and automaticity within isolated ventricular muscle strips. Chlorobutanol affected neither positive nor negative treppe. We conclude that bradykinin has no direct action on toad, frog, or rat myocardium. However, chlorobutanol does have direct effects on myocardial cells, acting on the cell membrane and decreasing isometric tension produced by the heart.


Inheritance of acute anterior uveitis and HL-A antigen 27. A family study on the inheritance of HL-A antigens and susceptibility to acute anterior uveitis is reported. In the 4 families examined, the antigen 27 (haplotype 2.27) occurred in all of the 7 patients with acute anterior uveitis and in 22 of the 33 healthy family members examined. It is suggested that in Finns the haplotype 2,27 is linked with genes predisposing the carrier to acute anterior uveitis.


[The influence of cortisone upon the metabolism of surviving lens epithelia and iris tissue (author's transl)]. Warburg experiments showed the oxygen consumption by lens epithelium and iris tissue without and after addition of 4 mg methylprednisolone to 100 cc medium. In the last case the O2-uptake of the epithelium seemed diminished, that of the iris tissue showed significantly reduced to 50%. The determination of the consumption of glucose was done by measuring its level in the medium before and after a 5 day's incubation, without and after addition of 4 mg-% of methylprednisolone, by means of the "Merckotest". The consumption of the epithelia lowered to 1/6; contrarily rose that of the iris tissue significantly to the double amount. The metabolism of the iris tissue showed a good adaptation in compensating a lower respiratory activity by a augmented glycolysis, which is impossible to the lens epithelium. This may be one of the factors inducing a cortisonic cataract.


[End position nystagmus caused by prolonged lateral gaze (author's transl)]. Electronystagmograms were recorded from six normal subjects who had to maintain an extreme sideward gaze either in the dark or using a fixation target. End position nystagmus occured in three subjects immediately, in two subjects with a latency of several seconds, and in one subject with a latency of 90 seconds. The nystagmus was typically dissociated and was similar whether the subject viewed a fixation point or was recorded from in darkness.


Ocular involvement in I-cell disease (mucolipidosis II). Light and electron microscopic findings. A 5 1/2 year old boy with I-cell disease (mucolipidosis II) had bilateral corneal haziness, early cortical cataracts and bilateral prominence of his eyes associated with shallow bony orbits. He died of pneumonia at age 5 1/2 years. Light and electron microscopic examination of the ocular and orbital tissues revealed an accumulation of acid mucopolysaccharide positive, hyaluronidase resistant material in fibroblasts and histiocytes which had partially replaced Bowman's membrane and the anterior stromal cells of the cornea. Similar material, as well as glycolipid-like substance, was found in the conjunctiva and in the retrobulbar soft tissues.


[Enzymatic studies in lenses of different breeds of mice (author's transl)]. Leucinaminopeptidase (LAP), lactatedehydrogenase (LDH) and glucose-6-phosphatdehydrogenase (GPDH) were analysed in the lenses of two different breeds of mice. Compared to the lenses of a control stock (Agnes Blum, Jena), in the healthy seeming, heterozygous mice the same activities of LAP, LDH, and GPDH were found. But in the breed with evident microphthalmos and cataract LDH was increased. Possible connections are discused.


Measurement of intraocular pressure: a study of its reproducibility. Intraocular pressure was measured with Goldmann applanation tonometers by two independent examiners in 420 eyes. A difference between measurements of at least 3 mm Hg occurred in 30% of the eyes. Some evidence suggests that the differences between pressure measuremens were caused by actual changes of intraocular pressure rather than by instrument inaccuracy of technician error.


A method for DC-ERG recording of alert humans. We developed a technique for DC-coupled ERG recording of the alert human. The equipment consists of three units: a new cornea suction glass, a separate electrode, and a vacuum control device. We get stable recordings of more than one-half hour. By comparison with the EOG the identity of the EOG "on"-peak and ERG c-wave is assured. A fine structure of DC-ERG recording of 100 muV amplitude is closely correlated to the variation of the blood pressure in the ophthalmic artery. It may either be caused by the variable electric conductivity of the eyeball due to the blood pressure or it may reflect a variation of the retinal potential itself.


[Standardized fluorescein injection in serial angiography (author's transl)]. Maximal initial dye concentration in the retinal arteries is desirable for high quality fluorescein Angiograms and is essential for circulation studies. Such high initial dye concentrations can only be achieved by a very rapid fluorescein injection technique necessitating an automatic injector. A reliable easy to use "spring-injector" has been designed for clinical use (Figs. 1 and 2). A disposable syringe is driven by a spring contained in a metal cylinder. Microswitches are activated by the piston of the injector triggering one exposure each at the beginning and at the end of the injection. Time and duration of the injection are therby permanently documented on the film. The "Terumo Disposable Syringe 10 cc" is used routinely. By interposing a plastic connector between syringe and injector-piston the injection-volume can be reduced to 5 ml. With diffferent connectors one can inject an volume desired up to 10 ml. The duration of the injection can be varied by using different intravenous catheters. Routinely the "VYGON Trocaflex catheter Nr. 125.16" with a needle diameter of 1.1 mm and a length of 30 cm is used resulting in an injection time of 10 ml/1.0 sec or 5 ml/0.5 sec. The largest Trocaflex catheter (No. 125.20) will shorten the injection time to 10 ml/0.5 sec and 5 ml/0.25 sec respectively. Even faster injections can be achieved by shortening the catheter or by using a stronger spring. With the described injector, high-speed, well-standardized fluorescein injections are possible. The intravenous catheter makes parvenous injections impossible and will allow for repeated angiograms even on different days without the need for a new venous puncture.


[Dendritic lesions in herpes simplex infection of the cornea. Scanning and transmission-electron microscope findings (author's transl)]. Thirty rabbits were divided into 10 groups of 3 animals. In the case of each animal 1 drop of Herpes virus hominis suspension (HVH) was applied to the intact cornea of the right eye. Within the period between the 2nd and 20th day after infection occurred, three animals were killed each time and the corneae were examined by scanning- and transmission-electron microscope. Circular foci and dendritic lesions were observed starting with the 4th day. After the 12th day, dendritic lesions could no longer be observed. Circular foci and dendritic lesions possess a width of about 200 mu which remains unchanged during the entire observation period. The areas of ulceration are obscured by lateral epithelium migrations. The observation that epithelial lesions do not change their demensions over an extended period of time, speaks for an approximate time balance between cellular damage caused by the viruses and the migratory speed of the epithelium. This mechanism is disrupted in the neighboring circular foci. The cytotoxic effect is predominant. Circular foci are confluent. The dendritic lesion so characteristic for herpes simplex infection of the cornea is explained by the confluence of several circular foci which are accidentally positioned next to each other.


Observation of injected fluorescein diffusion after laser treatment of cat fundi. An experimental study with angiography and microscopy. Argon laser coagulations with a power of 100 mW and 300 mW, exposure time 0.02 and 0.02 sec, and constant spot size of 100 microns were applied on normal cat fundi. From 1 and 2 hrs to 7 days after the coagulation, the treated eyes were observed angiographically and by fluorescence microscopy after dye injection; freeze dried eyes were examined under a fluorescence microscope. Abnormal dye leakages originated from the chorid and from retinal vessels were detected in the specimens examined within 72 hrs after the coagulation.


[Keratoprosthes made with soft plastic material--first experiments on animals (author's transl)]. To improve the nutrition of corneal tissue and decrease the extrusion rate in keratoprosthesis we developed implants made with HEMA (hydroxy-ethyl-methacrylate) and inserted these models in rabbit eyes. This soft hydrophilic material seemed to be suitable for intraocular implantation because of its permeability to small molecules, necessary for the nutrition of cornea, and because of its flexibility. Keratoprosthesis with these implants was performed on 30 rabbits. During an observation period of 21 months we did not observe any typical extrusion of the implant. Furthermore it was favorably noted that after insertion of the dehydrated prosthesis the HEMA, enlarged by water absorbtion, developing a close contact to the surrounding corneal tissue. The risk of infection with HEMA keratoprostheses is probably not increased. Further investigations are being performed.


[The alteration of visual evoked potentials in light- and dark-adapted states as a measure for the visual field sensibility at elevated intraocular pressure (author's transl)]. On 12 voluntary subjects with normal visual function the intraocular pressure was increased dependent on the ophthalmic blood pressure Pm = (Ps + Pd)/2. The visual field was tested under this pressure load by means of a subjective method and the visual evoked potential was derived under light and dark adaptation. Comparison of subjective and objective investigations demonstrated that the different visual evoked potentials which are dependent on the state of adaptation are a measure for the pressure sensibility of prelaminar optic nerve fibers.


[Microbiologic Investigations of experimental keratoprostheses made with hydrophilic plastics (author's transl)]. The subject of our investigations is the question: is there an increased risk of infection with eyes operated on keratoprostheses made with hydrophilic soft plastic material (HEMA)? Our first step was an analysis of the normal conjunctival spectrum of microorganism of our rabbits, operated and nonoperated. Then we made exploratory punctures of the anterior chamber of 7 eyes submitted to implantations of HEMA keratoprostheses. During a period of 10 days this puncture exudate was incubated in a culture medium. In 6 out of 7 cases, even after 10 days of incubation, no microorganisms were found. In one case after 72 hours of incubation, a poor growth of a staphylococcus was observed. It can be assumed that in this case the microorganism entered the anterior chamber during the puncture procedure. The results of these investigations confirm the calculation that the "pores" of hydrophilic plastic material are too small for penetration of microorganism.


[Quantitative determination of antiproteinases in human tears (author's transl)]. By quantitative determination of antiproteinases, i.e. alpha1-antitrypsin, alpha1-antichymotrypsin, and inter-alpha-trypsin inhibitor normal values could be obtained. The importance of antiproteinases is demonstrated in this paper. Especially alpha1-antitrypsin was very easy to quantitate and might be of diagnostic interest.


[A contribution for recording data in strabismus (author's transl)]. The recording of the data of all investigations in strabismus concomitans convergens is done by a formular, which is presented in this paper (Fig. 1). The data code is printed on  the backside (Fig. 2). It is possible to evaluate the results with this formular in a computer by punch cards. A quick information without computer help is possible as well. The methods of recording data used by different authors are explained and the advantages and disadvantages are discussed.


[Results of surgical treatment in strabismus convergens (author's transl)]. In 252 patients with strabismus concomitans convergens the surgical method of the combined medial rectus recession and lateral rectus resection (Fig. 1) was studied retrospectively. The reduction of the deviation was compared with the added displacement of both muscles (Figs. 2 and 3) or the displacement of one single muscles (Table 1 and 2). Fig. 4 shows the relation between the recession-resection and the reduction of the deviation. A formula for this reduction (Z) is given: Z=6.7 chi recession (in mm) + 2.2 chi resection (in mm) - 8.1. In long the recession is 3 times more effective than the resection. In 61.5% of the patients the eyes stood parallel after surgery or a residual deviation up to 5 degrees was achieved. There was a little difference in the total results of the first (1 week) and the second (6 months) postoperative control. Major differences occurred when comparing single data.


HLA-compatible donor cornea for prevention of allograft reaction. Our series comprises 80 penetrating grafts. Of the recipient corneas 36 were vascularized. Of the donor corneas 48 were fresh and 32 were cryopreserved. As prophylaxis, we gave topical and systemic prednisolone, combined, in heavily vascularized cases, with azathioprine. Corneal donor-recipient pairs were divided into three groups according to HLA histocompatibility. In Group I  (0-1 mismatch) the rate of allograft reaction was 1 in 27, in Group II (2-4 mismatches) it was 4 in 19, and in the untyped Group III 9 in 34. Even when the prognosis was poor, a well-matched donor cornea (Group I) greatly improved the chances of success; when the corneal bed was vascularized, the well-matched donor corneas had a failure rate of 1 in 13, whereas in untyped pairs it was 7 in 18. The importance of possible presensitization is discussed.


Glaucomatous cupping of the human optic disk: a neuro-histologic study. The optic nerve and optic disk in 20 cases of glaucoma were examined neurohistologically. The interruption of retinal axons was found localized in a narrow transversal strip at the level of the posterior part of the lamina cribrosa and immediately behind it. Retinal axons anterior to this zone were mostly intact as long as their ganglion cells of origin were preserved. This picture was essentially identical in cases of primary and secondary glaucoma. The significance of this finding is discussed together with some hypotheses on the origin and causes of the glaucomatous cupping of the optic disk.


The influence of age on the chronatic aberration of the eye. The axial chromatic aberration of the eye was measured in 58 persons varying from 10 to 80 years of age. It was found that the chromatic aberration diminished significantly after the onset of presbyopia. It is suggested that this decrease in axial chromatic aberration may be due to increase in the index of refraction of the vitreous thereby producing a negative optical surface in the eye which more or less cancels the chromatic aberration of the cornea and anterior surface of the lens. This supposition is supported by measurements of chromatic aberration made on 10 aphakic patients. It is also observed that at near, older eyes who exhibit very little chromatic aberration, cannot make use of this aberration to spare some of the required accommodation (simulated by ophthalmic lenses in older eyes) as is the case in younger eyes.


[The accuracy of ophthalmodynamometry in the diagnosis of occlusions of the carotid artery (author's transl)]. The aim of this study was to evaluate the diagnostic accuracy of ophthalmodynamometry in cases of occlusion of the internal carotid artery. Among the 29 patients examined with ODM there were 12 cases of such an occlusion, which were unknown to the ophthalmological examiner. All of them could be diagnosed exactly. When by means of ODM an occlusion in the region of the common or internal carotid was excluded the result was equally accurate. A decrease in ophthalmic blood pressure by 15% or a side difference of the same degree indicated in 80% of the cases an occlusion of the internal carotid. The ODM seems, therefore, to be a suitable test for finding or excluding such an occlusion.


[ERG- and EOG results in the vitreo-retinal syndrom of Jaffe (author's transl)]. An ERG and EOG were performed in 2 cases of Jaffe's vitreo-retinal traction syndrom with differing stages of the disease. In the first stage of the disease there was a crease in the b-waves in the presence of a normal EOG. In stage II there was a beginning leveling of the ERG with gradual disappearance of the x-waves and b1-waves in the presence of the subnormal EOG. In stage III, there was a clear discrepancy between the monophasic ERG with deep a-wave and smooth b-waves, and the subnormal EOG, thus indicating damage to the retinal vascular system which is important for the nutrition of the III neurons.


ERG of humans without C-wave.

ERG of humans without C-wave. Three out of 18 healthy persons investigated with the DC-ERG do not show a c-wave. By varying the adaptation levels and intensities of the stimuli four components in the human ERG can be isolated, the cone and rod late receptor potentials, the positive DC response, and a c-wave in most subjects. It is suggested that investigation of these components reveals a more detailed understanding of the pathophysiologic mechanisms in some retinal diseases.


[Measurements of the maximal excursion-ability of the globe (author's transl)]. Method and results of measurements of the maximal version movements by using a millimeter graduated scale after Kestenbaum are descripted. We prefer a millimeter net scale formed as a spectacle. In this way measurements can be done in an accuracy of +/- 0.5 mm about.


[Myocardial contractility in dogs in hemorrhagic shock and after volumn replacement (author's transl)]. Myocardial contractility was evaluated in 8 out of 14 anaesthetized mongrel dogs during haemorrhagic shock and after volume replacement with Dextran 60 using the force-velocity relation of the contractile elements at zero load (Vmax). 7 animals received 50,000 or 20,000 KIE respectively of a proteinase inhibitor after bleeding and immediately before and one hour after the infusion of Dextran 60. The release of the lysosomal enzymes acid phosphatase and beta-glucuronidase was inhibited significantly (p less than 0.05) in the animals treated with Trasylol. However, the inhibition of the lysosomal enzymes seems not to have a decisive influence on the dynamic of the macro- and microcirculation and the myocardial contractility.


Influence of adrenalectomy, total body x-irradiation and dexamethasone on the amount of CRF-granules and "classical" neurosecretory material in the rat neurohypophysis. In 195 female Wistar rats the influence of adrenalectomy, total body X-irradiation and dexamethasone treatment on the amount of CRF-granules in the external zone of the median eminence and "classical" neurosecretory material (NSM) in the internal zone of the median and in the posterior lobe of the hypophysis has been studied. In the normal rat only very few CRF-granules occur. 15 days after adrenalectomy increased amounts of CRF-granules but normal amounts of "classical" NSM are found. X-irradiation leads to a slight diminishment of "classical" NSM in normal rats. In adrenalectomized animals X-irradiation causes no changes in the amount of "classical" NSM but a marked decrease in the amount of CRF-granules. Application of dexamethasone from the 15th to 18th day after adrenalectomy enhances the augmentation of CRF-granules in irradiated and non-irradiated rats but does not influence the amount of "classical" NSM. The findings show that no correlation exists between the quantitative changes of CRF-granules and "classical" NSM under the experimental conditions used. Therefore it is to be assumed that the release of the two substances is regulated by different control mechanisms and that the substances have a different functional significance. The observations do not exclude the possibility that CRF-granules and "classical" NSM are biochemically identical.


High prevalence of antinuclear antibodies in sandblasters' silicosis. Of 39 silicotic sandblasters evaluated in 1972 and 1973, 17 (44 per cent) had positive serum antinuclear antibody reactions. This prevalence is higher than those reported for other pneumonconioses. Comparison of the groups positive and negative for antinuclear antibodies showed that patients positive for antinuclear antibodies were unlikely to have normal ventilatory function and were more likely to have roentgenograms showing large opacities. Both groups had similar proportions showing lobar cavitation or contraction.


Incidence of prolonged pain relief following acupuncture. From March 1973 to Decenber 1974, 2090 electroacupuncture treatments were applied to 533 patients with chronic pain. Of 533 patients, 276 (52%) reported excellent (greater than 75%) pain relief immediately after the last treatment, and 103 (19.3%) still reported excellent pain relief on a 4-week followup questionnaire. In March 1975, the authors contacted 87 of these 103 patients. Sixty-three reported that they still had excellent pain relief 3 to 18 months after therapy, 3 patients reported that their pain still was relieved 50%, and 21 patients said their pain had returned to the same intensity as before therapy. Thus, 12% of 533 patients who received acupuncture treatment for chronic pain had a significant degree of pain relief at least 3 months after therapy.


Some dielectric properties of muscle membrane and their possible importance for excitation-contraction coupling. Voltage-clamp studies of polarization currents have shown the presence of polar molecules in the membrane of skeletal muscle. Their high dipole moment and favorable transition potential suggest that they may be "gating molecules" which serve to regulate some membrane potential-dependent physiological function. Experiments with the drugs tetrodotoxin and tetracaine show that these polar molecules are unlikely to play a role in regulating the sodium and potassium channels responsible for electrical excitation. Instead, they may regulate calcium release from the sarcoplasmic reticulum, which also depends steeply on the cell membrane potential. Schneider and Chandler's hypothesis whereby calcium release from the sarcoplasmic reticulum is regulated by voltage-sensitive "gating molecules" in the tubule membrane is still unproven, but remains attractive and plausible.


Some electronystagmographic manifestations of central nervous system disease. A battery of tests with electronystagmography were performed on two groups of patients, one in which posterior fossa abnormalities had been confirmed independently by neurologic findings, contrast studies, or surgery; the other group consisted of what seemed clinically clear cut peripheral VIII nerve or labyrinthine disturbances. The two groups were compared statistically for the incidence of factors thought to indicate the presence of brain stem lesions. No single factor is absolutely reliable by itself as an indicator of brain stem disease, but the use of a test battery permits a much more accurate indication of probability of the presence of brain stem lesions.


Vestibular decruitment in central nervous system disease. The differential caloric test consisting of a weak and of a strong stimulation may provide evidence of certain vestibulo-oculomotor abnormality. The phenomenon of vestibular decruitment serves as an indication of central nervous system or intracranial pathology. A classification of the degree of decruitment was attempted in 139 patients exhibiting this phenomenon. Ample evidence is provided that vestibular decruitment is indicative of a variety of intracranial lesions predominantly in the posterior fossa. Decruitment was encountered with hypo- and hyperactive vestibular responses alike and also in patients in whom there was no deficit in end organ sensitivity. The armamentarium of neurotologic testing is enriched by the differential caloric stimulations providing an indication  of the "site of lesion."


Temporal bone histopathology of osteopetrosis. The histopathology of the temporal bone of an eight and one-half-year-old girl with osteopetrosis (Albers-Schönberg disease) was studied to evaluate the pathogenesis of its frequent complications in hearing and facial nerve function. The patient was blind and had acute otitis media, but facial paralysis was not noted. Although the size of the temporal bone pyramid was markedly increased due to enormously thickened periosteal layer, changes in the endosteal and endochondral layers  were less marked. Exostotic growth of periosteal bone was seen in the middle ear wall, and the tympanic cavity appeared to be narrowed. At the oval window region, the facial nerve was pushed down towards the stapes due to extreme overgrowth of periosteal bone of the epitympanum, and the superstructure of the stapes was imbedded deeply into the dislocated facial nerve and had strongly compressed it. Although the footplate was free from ankylosis, the crus of the stapes appeared to be immobilized because it was lodged in the facial nerve. Such changes appeared to be the pathogenesis of one form of facial nerve paralysis and conductive hearing loss associated with osteopetrosis.


[Trisomy 10q24--10qter].

[Trisomy 10q24--10qter]. The syndrome of trisomy 10q24leads to 10qter is described from three patients studied by the authors and five cases reported from the literature. The characteristic dysmorphy of the syndrome, although different from that of trisomy 21, nevertheless is reminiscent because of euroasiatic facies. The facies is broad, round, because of euroasiatic facies. The facies is broad, round, and flat, with a prominent malar region and a high and convex forehead. Palpebral fissures are narrow with bilateral epicanthal folds, and the nasal bridge is hypoplasitc. Marked joint laxity allows spontaneous and reductible subluxations. Growth retardation is the rule, and mental retardation is severe. No specific dermatoglyphic abnormalities are noted; there is a gap between the first and second toes, with a marked plantar crease separating them. Although trisomy 10q24leads to10qter results from various terminal translocations or pericentric inversion in one case, the location of the breakage point in band 10q24 suggests a particular lability of this zone.


[Prevalence of etinoblastoma in the Midi-Pyrenées area]. The frequency of retinoblastoma was estimated in southwest France (Midi-Pyrénées) during the 1950-1969 period. Twenty-three cases were detected among 507 157 liveborns. After correcting for the probability of ascertainment of patient, the estimated frequency is 1 per 15 849 births. The proportion of unilateral cases is estimated 91 percent after correcting for the higher probability of ascertaining bilateral cases.


[Pericentric inversion of no. 3, homozygous and heterozygous, and centromeric transposition of no. 12 in a family of orangutans. Implications for evolution]. An orang-utan family is reported in which the father (Piku) is homozygous for a pericentric inversion of chromosome 3 and heterozygous for a structural rearrangement of chromosome 12 (author's nomenclature for this species). The latter is interpreted as transposition of the centromere by insertion into band q213 [ins cen(12)(q213)]. Piku's mate has a normal female chromosome complement. His daughters by this mate (Agnès and Ursula) are heterozygous for both his rearrangements. A fifth orang-utan (Arnold) captured on a different Malesian island was found to have one chromosome 12 similar to that of Piku, and to have a female complement, even though his keapers considered him male. Several hypotheses are proposed to explain the observations, including consanguinity, the existence of a common polymorphism in the species, and the existence of an established subspecies among orang-utans.


Identification of isochromosome 17 in a girl with mental retardation and congenital malformations. An isochromosome 17 was found in all analyzed cells of a mentally retarded and malformed girl. As the abnormal chromosome displayed a polymorphic distal band also observed in chromosome 17 of the father, it is suggested that the abnormal chromosome is the result of a non sister chromatid interchange at the level of the centromeric region of chromosomes 17 in paternal meiosis.


Chromosome band analysis in 19 cases of chronic myeloid leukemia: 9 chronic, 10 blastic, two with Ph1 (22q-) translocation on 17 short arm. The results of Giemsa band analyses of the marrow cells of 19 cases of CML in the chronic or blast phase are reported. All but one of the 14 Ph1 positive cases showed the 9q+pattern, the exceptional one being 16p+. All 10 blast cases showed additional rearrangements, which are described. In two of the cases, one blastic, one chronic, which were -22, Ph1 negative, the 22q- member was identified as a translocation on the short arm of one 17 which was dicentric.


Coagulation studies in patients with trisomy 8 syndrome. Coagulation studies were performed in three patients with trisomy for chromosome No. 8. In contrast to the findings reported by others, all patients were found to have a normal coagulation status without sign of factor VII deficiency.


[A second example of telomeric fusion 2 X chromosomes]. A translocation which originated by telomeric "fusion" of X short arms, t(X;X), was found in a woman with primary amenorrhea and a phenotype corresponding partially to Turner's syndrome. Staining with acridine orange after BrdU incorporation showed the distal segments of both Xp's to be much more modified by the treatment than equivalent segments of normal late replicating X's. This could mean important inactivation of segments usually active even in late replicating X's. This functional monosomy for X would have a clinical effect similar to a true monosomy.


[Partial 11q monosomy and trigonocephaly. A new syndrome]. Partial monosomy 11q occurring de novo and concerning the 11q231 leads to qter region, is reported in a 2-month-old boy. This observation together with three others from the literature allows the individualization of a syndrome characterized by: severe growth retardation: more or less pronounced mental retardation; trigonocephaly; facial dysmorphia.


Susceptibility of Haemophilus influenzae isolates from blood and cerebrospinal fluid to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole. Susceptibility to ampicillin and chloramphenicol in vitro has been determined for Haemophilus influenzae strains isolated from blood and/or cerebrospinal fluid cultures of patients admitted to two Atlanta hospitals from 1 January 1974 to 31 March 1975. Since the appearance of ampicillin-resistant strains of this organism in early 1974, chloramphenicol has been used in these hospitals as initial therapy for severe infection due to H. influenzae. Strains from five of 94 patients were resistant to ampicillin (minimum inhibitory concentration [MIC] >/= 12.5 mug/ml), but all strains were susceptible to chloramphenicol (MIC < 2 mug/ml). The first 35 strains studied, including three resistant to ampicillin, were also tested for in vitro susceptibility to trimethoprim-sulfamethoxazole; all were highly susceptible (MIC </= 0.0312 mug of trimethoprim and 0.625 mug of sulfamethoxazole per ml).


Mechanisms of ampicillin resistance in Haemophilus influenzae type B. The genetic mechanisms associated with ampicillin resistance in strains of Haemophilus influenzae type b were investigated. In experiments concerned with transfer of total deoxyribonucleic acid in vitro, expression of resistance by wild-type strains occurred at a frequency of about 10%. The minimum inhibitory concentration of ampicillin for the transformed strains was similar to that of the resistant donor strains, and resistance in transformants was associated with acquisition of the ability to produce beta-lactamase. Exposure to 39 mug of acridine per ml for 18 h cured resistance at a frequency of 80%, and there was spontaneous loss of resistance after repeated subculture of some strains. Analysis by cesium chloride-ethidium bromide density gradient centrifugation demonstrated the presence of extrachromosomal deoxyribonucleic acid in the resistant strains, providing further evidence that the resistance factor is plasmid mediated.


Susceptibility of Haemophilus influenza to ampicillin as determined by use of a modified, one-minute beta-lactamase test. Fifty-seven cultures of Haemophilus influenzae were tested for production of beta-lactamase by use of a modified, 1-min test. Only the 24 cultures that were ampicillin resistant, whether type b or not, yielded positive results for the enzyme; all ampicillin-susceptible isolates were uniformly negative. The beta-lactamase procedure is simple to perform and requires only commonly available reagents.


Spurious ampicillin resistance by testing Haemophilus influenzae with agar containing supplement C. Ampicillin resistance (minimal inhibitory concentration >/=10 mug/ml) in the absence of beta-lactamase activity by Haemophilus influenzae was noted in tests performed with Mueller-Hinton agar containing one lot of supplement C. All strains, except five with known resistance due to beta-lactamase activity, were inhibited by 0.6 mug or less of ampicillin per ml of chocolatized blood agar.


Susceptibility of ampicillin-resistant Haemophilus influenzae to seven penicillins. Sixty-seven clinical isolates of Haemophilus influenzae from various sections of the United States, England, and Germany were tested for susceptibility to penicillin, ampicillin, amoxicillin, epicillin, carbenicillin, ticarcillin, and methicillin. Fifty-three of the strains had previously been judged to be ampicillin resistant and 14 had been determined to be ampicillin susceptible. Fifty-two of the 53 resistant strains produced beta-lactamase, but none of the susceptible strains produced it. On the basis of minimal inhibitory concentrations, the most active compounds were ticarcillin and carbenicillin. Whether this greater activity is useful clinically has not been established.


A new species of the genus Bullera derx. A new yeast species, Bullera piricola, is described. The three strains studied were all isolated from the pear phylloplane. This species differs from all Bullera species known at present by forming symmetrical as well as asymmetrical ballistospores. The problem of its integration into the genus Bullera Derx is discussed. An amended diagnosis of the genus Bullera is given.


The amino acid pool of Hansenula holstil: characterisation, and changes mediated by environment. Amino acid pools extracted from Hansenula holstii grown in continuous culture with either ammonia or nitrate as sole source of nitrogen, under a variety of substrate limitations, were characterised and quantified. Pools from corresponding cultures were shown to be similar in size and composition, regardless of whether ammonia or nitrate was the nitrogen source. Large changes in pools (both quantitative and qualitative) occurred when cultures were grown under different substrate limitations. Such changes were particularly large in glutamate, glutamine, alanine, lysine and arginine; the possible significance of such environment-mediated changes is discussed.


Oxidation of organic C1 compounds by Hyphomicrobium spp. Washed cell suspensions of Hyphomicrobium spp. were able to oxidize methanol, formaldehyde and formate. This suggested that enzymes for the oxidation of these compounds were present. The pathway of the oxidation of methanol to carbon dioxide and water has been investigated using cell-free extracts. An ammonium-ion-activated, phenazine methosulphate-linked methanol dehydrogenase was detected. This enzyme has a dual substrate specificity for normal primary alcohols and formaldehyde. It has a high pH optimum for activity of 9.5. The pathway is completed by an NAD-linked formate dehydrogenase. This enzyme is inhibited by low concentrations of potassium cyanide, copper sulphate and hypophosphite.


Production and characterization of the agarase of Cytoplaga flevensis. Cytophaga flevensis produced an inducible agarase which was extracellular under most conditions tested. The effect of cultural conditions on the production of enzyme was studied in batch and continuous culture. In batch culture, production was optimal when Cytophaga flevensis was incubated at 20 C in a mineral medium with agar as the sole carbon source and ammonium nitrate as the nitrogen source at an initial pH of 6.6-7.0. The enzyme appeared to be subject to catabolite repression, since its synthesis was repressed when glucose was added to the medium in batch culture. Furthermore, in continuous culture, enzyme production decreased with increasing growth rate. Extracellular agarase was partially purified and the enzyme preparation obtained was very stable. The enzyme has a molecular weight of 26 000 daltons. It is a beta-agarase which is highly specific for polysaccharides containing neoagarobiose units. The final products of hydrolysis of agarose by the endo-acting enzyme were neoagarotetraose and neoagarobiose. Optimal conditions for its activity were pH 6.3 and 30C. When agarose was used as a substrate, an apparent temperature optimum of 35C was found, due to gelling of the substrate during the assay procedure.


Oxalate and formate in Alcaligenes and Pseudomonas species. Oxalate is metabolized by the glycerate pathway involving glyoxylate carboligase in Alcaligenes LOx and Pseudomonas KOx, and by the serine pathway involving hydroxypyruvate reductase in Ps.MOx and Ps.AM1 (var. 470). Although A.LOx does not grow on formate, stimulation of growth was observed in the presence of amino acids and a few Kreb's cycle intermediates. A.LOx possesses two different mechanisms for the oxidation of formate: (1) the constitutive formate oxidase which is present in the particulate fraction of oxalate-grown and succinate-plus-formate-grown cells; (2) the inducible NAD-linked formate dehydrogenase present in the 100 000 x g supernatant fraction of the cell-free extracts of oxalate-grown cells alone. The two systems occur simultaneously in oxalate-grown cells. The effect of inhibitors on formate oxidase activity and the other enzyme activities of the particulate formate-oxidizing fraction indicate that the oxidation of formate is linked to the respiratory chain.


Microbial degradation of piperonylic acid. Several organisms were isolated for their ability to utilize piperonylate as a sole carbon source for growth and a Pseudomonas species (Ps. PP-2) was selected for a study of the degradation of this substrate. Only vanillate, isovanillate, p-hydroxybenzoate and protocatechuate, of several possible catabolities, served as growth and oxidation substrates for the organism. Detailed analysis of the culture fluid from piperonylate-grown cells revealed the presence of vanillate and protocatechuate but isovanillate, p-hydroxybenzoate and m-hydroxybenzoate were not detected. The evidence presented suggests that piperonylate is metabolized first to vanillate by methylenedioxy ring cleavage and next to protocatechuate by direct dimethylation of vanillate.


The role of plant particles, bacteria and cell-free supernatant fractions of rumen contents in the hydrolysis of trilinolein and the subsequent hydrogenation of linoleic acid. The role of different fractions of rumen contents in the hydrolysis of trilinolein and the subsequent hydrogenation of the linoleic acid has been investigated by a series of in vitro incubations. Hydrolysis of the trilinolein to free linoleic acid occurs almost wholly in the cell-free supernatant; the liberated linoleic acid in the supernatant can be rapidly adsorbed onto food particles where it is hydrogenated to stearic acid via the C18 trans-11 monoene. Some 25% of the trilinolein added as substrate was taken up by the bacteria and of this a small percentage appeared to be hydrolysed and the free linoleic acid hydrogenated to stearic acid intracellularly. No conclusive evidence was obtained to suggest that this intracellular hydrogenation proceeded by a route other than that which took place on the food particles.


Methanobacterium arbophilicum sp.nov. An obligate anaerobe isolated from wetwood of living trees. The isolation and characterization of a new methanogenic bacterium, Methanobacterium arbophilicum, is described. Isolation from wetwood enrichment cultures, that were obtained from methane-positive trees, required a medium containing inorganic salts, vitamins, and an atmosphere consisting of an 80:20 mixture of hydrogen-carbon dioxide. Isolates of M. arbophilicum were gram-positive, non-motile short rods that occurred singly, in pairs, or chains. The organism was found to be an autotroph and a strick anaerobe, and to have a pH optimum of 7.5-8.0. The optimal temperature for growth was 30 to 37C, the maximum being 45C and the minimum about 10C. The organism had obligate growth requirements for H2 and CO2, and organic compounds greatly stimulated growth. The generation time in shake flask culture was about 17 hr in mineral salts medium and about 13 hr in complex medium. The DNA base composition was 27.5 mol % GC.


Characteristics of weak H2S-producing isolates of Pseudomonas putrefaciens from human infections. Isolates from human clinical specimens which produced salmon-colored colonies were found to grow at 2C and produce ornthine decarboxylase, DNase, trimethylamine and only slight amounts of H2S. The notably weak ability of such isolates to produce H2S was originally regarded as a negative reaction. The DNA base composition of such isolates was found to range from 48.3 to 49.2 moles % GC. These observations, along with bacteriocin typing, resulted in identification of the isolates as Pseudomonas putrefaciens.


Galvanic vestibular stimulation.

Galvanic vestibular stimulation. In order to gain insight into the origin of the eye movements provoked by galvanic vestibular stimulation, experiments were conducted in rabbits. The animals were subjected to a small galvanic stimulation and to a vestibular stimulation (rotation and sinusoidally changing linear accelerations). Application of several stimuli at the same time shows that the effects on the eye movements of each stimulus given separately are summated. Electric stimulation provoked vestibular reflexes; a stronger effect was observed in unilaterally and in bilaterally labyrinthectomized rabbits. This suggests that there is not only an impact of the oculomotor system but of the peripheral vestibular organs too. The conclusion is drawn that electric stimulation of the vestibular system gives information on the functioning of the labyrinths and also about the side where a labyrinthine lesion is located.


Familial dysequilibrium-diplegia with T-lymphocyte deficiency. A second family is described with a combination of defective thymus-dependent immunity and cerebral palsy. The cerebral palsy comprised nonprogressive dysequilibrium and mild spastic diplegia without limb ataxia. This genetic entity of presumed autosomal recessive inheritance is clearly distinguished from ataxia-telangiectasia. Immunological abnormalities should be sought in other familial or unexplained cerebral palsy syndromes.


Benign rectal ulceration of unknown origin. An unusual cause of rectal bleeding. An unusual progressive form of benign rectal ulceration was found in an infant who presented with repeated episodes of rectal bleeding. The ulceration failed to respond to medical treatment but was cured by anterior resection of the rectum. The aetiology is not known.


Study of lymphoid cells from inflamed synovial membranes. Synovectomy specimens from patients with rheumatoid arthritis were cultured and after 24 hours the nonadherent cells were removed. These were found to include cells with the morphological characteristics of lymphocytes. Using the sheep-cell rosetting test, up to 94% of these cells were found to be T cells, and while T cells could be found in all the supernatant cell populations studied, not all made a mitogen response. None or only a very small number of B cells were found by staining for surface immunoglobulin. The possible roles which T lymphocytes might play in chronic inflammation in the rheumatoid synovium are discussed in relation to experimental work, and factors which attract T cells into areas of nonspecific inflammation are similarly considered in the light of animal experiments.


Pneumocystis pneumonia: the importance of early open lung biopsy. Pulmonary infection due to Pneumocystis carinii is now recognized as the leading cause of death from infection in patients with a hematologic malignancy who are in remission. Effective treatment requires suspicion of the infection in susceptible patients and rapid identification of the organism. In most patients, open lung biopsy performed through a small anterior thoracotomy provides immediate identification or exclusion of the organism, thus allowing treatment of infected patients and avoidance of inappropriate therapy in patients without the disease. We feel that the use of early thoracotomy, in spite of the fact that it exposes these very ill patients to a major surgical procedure and general anesthesia, is ultimately the safest therapeutic course.


Portosystemic shunting in patients with primary biliary cirrhosis: a good risk disease. Five patients with primary biliary cirrhosis underwent portosystemic shunting for the control of variceal bleeding. Three procedures were emergencies and two were elective. There was no operative mortality; all patients were followed until the present or until death. One patient is alive 4 years and another, 2 years postoperatively. One patient died 4 years after operation and another died 16 months postoperatively. Another patient survived for 8 years following her shunt and eventually died as a result of a cerebrovascular accident. This group of patients is compared to a larger group undergoing portosystemic shunting because of portal hypertension secondary to other forms of liver disease. The absence of operative mortality and the fact that several of these patients had moderately long postoperative survival despite apparently poor liver function suggest that the usual criteria for the assessment of operative risk are not valid in primary biliary cirrhosis.


Idiopathic late-onset immunoglobulin deficiency with functional T-cell deficiency. The common features in our two patients were late onset of infections that are known to complicate both T-cell and B-cell deficiencies, decreased numbers of circulating B-cells with low serum immunoglobulin levels, and normal numbers of circulating T-cells, which were, however, defective in the response to delayed hypersensitivity skin test antigens and to mitogens in vitro. The composite of clinical and immunologic aberrations is consistent with the presence of an immune deficiency involving the B-cell system quantitatively and the T-cell system qualitatively.


Interaction of 6,6'-dithiodinicotinic acid with rat thymocytes pretreated with thiol compounds. The number of sulfhydryl groups in the membranes of rat thymocytes were determined, expressed in terms of concentration of 6-mercaptonicotinic acid produced by reduction of 6,6'-dithiodinicotinic acid. The influence of incubation of thymocytes in solutions of L-cysteine, reduced glutathione and dithiothreitol on the number of -SH groups was studied. About twofold higher degree of reduction of 6-6'dithiodinicotinic acid was observed in the reaction with thymocytes incubated previously in 2 mM solution of L-cysteine in comparison with controls. Incubation of thymocytes with dithiothreitol and gluthathione had no effect on the number of -SH groups.


Activity of nonsteroid anti-inflammatory drugs in immunologically specific and nonspecific cellular responses. The influence of nonsteroid anti-inflammatory drugs on immunologic reactions of the humoral type (agglutinins, hemolysins) and of the cellular types (blast test, transplantation test), and on the course of immunologically nonspecific inflammatory reactions(xylene inflammation, pleurisy, granulation test) has been studied. Virtually regardless of chemical structure (indomethacin, mefenamic acid, acetylsalicylic acid, chloroquine), the drugs of this group had no influence on humoral responses, but a distinct influence on the delayed type of cellular responses and on immunologically nonspecific reactions. The investigated drugs had quantitatively varying modes of action, and only chloroquine showed a qualitatively different mode of action. It was concluded that nonsteroid anti-inflammatory drugs ace on a common link in inflammatory processes involving the immunologic system, as well as without such an involvement. The mechanism of their effect was considered to consist in stabilization of cell membranes, inhibition of proliferation and cellular transformation, and inhibition of the lymph node permeability factor (LNPF).


The right to know: giving the patient his medical record. Each patient  admitted to the 16-bed Rehabilitation Medicine Service at Medical Center Hospital of Vermont since October 1972 has received a carbon copy of his full Admission and Discharge notes, containing the complete problem list, and for each problem the relevant data, the Assessment and the Plans. The objectives were to improve patient education; to improve the patient's chances to contribute to the planning of his care; and to increase the staff's accountability to the patient. Over a period of seven months, we evaluated the effect of this maneuver for 125 consecutive patients by means of (1) a report on the patient's reactions, completed by a nurse after she reviewed the record with the patient; (2) a report by the physician stating whether he had expurgated the record for patient use, and recording his observations of patient and family reaction; (3) a questionnaire mailed to patients after discharge. Results indicated that patients were generally comfortable about reading the record, found it educational and appreciated the trust implied. No substantial difficulties arose. Few records were expurgated. The staff has accepted this style as crucial to an appropriate sharing of responsibility between themselves and the patients. We conclude that giving the patient his record is a safe and inexpensive aid to the rehabilitation process, and is probably mandated by the changing relationships between professionals and their clients, and by the patient's need to negotiate his own health care in an increasingly complex and mobile society.


Thermal injury in von willebrand disease. Management of burn wound bleeding. A 51-year-old woman sustained a 40% third-degree burn. After five grafting procedures that were unsuccessful due to uncontrolled bleeding, the diagnosis of von Willebrand disease was established. Skin grafting was subsequently accomplished without difficulty using cryoprecipitate as a source of antihemophilic factor (factor VIII). Serial clinical and laboratory investigations demonstrated that using the level of factor VIII procoagulant activity alone as an in vitro index of hemostasis was insufficient as a guide to the control of pathologic burn wound bleeding in this patient.


The endoscopic diagnosis of an aortoduodenal fistula. An aortoduodenal fistula is a serious complication of aortic reconstructive surgery. This artile describes a case in which the diagnosis of an aortoduodenal fistula was made by upper gastrointestinal endoscopy. The endoscopic finding of a vascular prosthesis within the duodenum allowed immediate surgical intervention and control of the gastrointestinal hemorrhage.


Treatment of reflux esophagitis resulting in massive esophageal bleeding. The complications that occur secondary to sliding hiatal hernia are reflux esophagitis with ulceration, stricture formation, and hemorrhage. We have treated seven patients for massive esophageal bleeding secondary to reflux esophagitis. All had endoscopic evidence of reflux esophagitis and a negative work-up for other sources of bleeding. All underwent Nissen fundoplication as the only mode of therapy for the bleeding esophagitis. No patient has bled again; healing of the esophagitis was evident six weeks after operation, as observed by gastrointestinal endoscopy. This operation prevents reflux, has minimal side-effects, and gives consistent results in the hands of the average trained gastrointestinal surgeon.


Primary duodenal tumors: a diagnostic and therapeutic dilemma. The case records of ten patients with benign, three with endocrine, and 19 with malignant duodenal tumors were reviewed. Patients with benign tumors had episodes of bleeding that were recurrent in a number of cases. The endocrine tumors were all gastrinomas; patients had ulcer diathesis associated with the Zollinger-Ellison syndrome. All malignant tumors were symptomatic, with chronic gastrointestinal blood loss or duodenal obstruction. All benign tumors were demonstrated preoperatively, but only ten of 19 malignant tumors were confirmed preoperatively. The data suggest that duodenal tumors masquerade as more common diseases and as a result, their diagnosis and treatment are delayed inordinately. Awareness of this problem is encouraged, and a more aggressive diagnostic effort in selected patients, including fiberoptic endoscopy, is suggested.


Arteriovenous malformations of the gastrointestinal tract. During an eight-year period, 17 patients ranging in age from 7 months to 81 years were found to have arteriovenous malformations (AVMs) of the gastrointestinal tract complicated by major hemorrhage. After review of these cases, a clinical classification of AVMs was developed, based on angiographic characteristics, localization, age of the patient, and family history. Type 1 AVMs were solitary, localized lesions within the right side of the colon. They occurred in seven patients 55 years of age or older. None were palpable or visible at operation. Type 2 AVMs occurred in seven patients. They were larger and occasionally visible, most commonly in the small intestine, and probably of congenital origin. Symptoms all began before 50 years of age. Type 3 AVMs were punctate angiomas causing gastrointestinal hemorrhage. They occurred in three patients with the classical findings of hereditary hemorrhagic telangiectasia. The diagnosis of most AVMs can be determined preoperatively only by selective angiographic studies.


Aortocoronary artery bypass: present indications and risk factors. From 1969 through 1974, a total of 4,522 patients were operated on for coronary artery occlusive disease. This article is an in-depth analysis of a consecutive series of 275 of these patients, operated on during 1974. The mortality was 1.8% and perioperative myocardial infarction occurred in 3.6%. On analysis of risk factors, it was found that 24% of the patients were over the age of 60; 57% had some degree of left ventricular dysfunction; 9% had generalized hypokinesis; 24% were New York Heart Association functional class IV; 13% had left main coronary artery stenosis; and 11% had preinfarction angina. On analysis of the early mortality, the limiting factor was diffuse coronary arteriosclerosis combined with poor ventricular function. This resulted in inadequate or incomplete myocardial revascularization. Since these two risk factors are usually predictable, coronary artery bypass can be recommended not only for patients with intractable angina, but also for patients with impaired left ventricular function associated with angina, and in patients without angina who have a positive stress electrocardiogram.


Left ventricular aneurysmectomy.

Left ventricular aneurysmectomy. Comparison of preoperative and postoperative studies in 81 patients undergoing left ventricular aneurysmectomy failed to show consistent hemodynamic trends. The most reliable prognostic indicator for survival (84% early, 71% late) was the function of the basilar ventricular segments. In 62 of the 81 patients, there was concomitant aortocoronary bypass grafting. Eighty-eight percent of the surviving patients are essentially free of symptoms. These findings support the continued surgical treatment of ventricular aneurysm in symptomatic patients, and suggest nonoperative treatment for patients who are asymptomatic.


Major arterial hemorrhage: a complication of pancreatic pseudocysts and chronic pancreatitis. Twelve patients (11 men, one woman), aged 18 to 68 years, had major arterial hemorrhage as a direct complication of pancreatic pseudocysts and chronic pancreatitis. Chronic alcoholism (11 patients) and blunt abdominal trauma (one patient) were the basis for pancreatic disease. Spontaneous hemorrhage occurred in eight patients. Bleeding occurred into the gastrointestinal tract (eight patients), into the peritoneal cavity (four patients), and was intracystic (one patient). Splenic, pancreaticoduodenal, gastroduodenal, and gastroepiploic arteries were sources of hemorrhage. Operative procedures included local control of bleeding (six patients), distal pancreatectomy (three patients), and pancreaticoduodenectomy (one patient). Four patients died of hemorrhagic complications of pancreatic disease, including one not subjected to operation. Extirpation of diseased pancreatic tissue may lessen the morbidity and mortality attributed to this complication of pancreatitis.


[Regeneration of the gastric mucosa under conditions of massive blood loss]. The autoradiographic method was used for a comparative study of regeneration of the gastric mucosa after wounding the rat with a preliminary loss of blood and without it. The H3-thymidin label index was determined in the portions of the mucosa of the wound edge and far from it. A histological analysis of healing the wounds failed to reveal any difference in terms of this process in rats with a loss of blood and without it. A momentary massive loss of blood did not influence the strain and intracellular regeneration processes in the healing wound of the stomach: the amount of cells synthesizing DNA at the edges of the gastrotonic wound proved to be the same in experiments both with a loss of blood and without it. The authors believe that it may serve as an indirect evidence of a somewhat exaggerated danger of surgery at the height of gastroduodenal bleeding.


Slow saccades in spinocerebellar degeneration. Two patients with spinocerebellar degeneration made abnormally slow horizontal refixations. One patient produced quick phases of nystagmus with identical maximum velocities, suggesting her refixations were abnormal saccades and not voluntary pursuit movements. In response to double target jumps, neither patient showed an obligatory refractory period after each saccade; they responded to every target movement after one reaction time. Their slow refixations were not preprogrammed since they could be modified in flight. To reconcile these observations with normal saccadic behavior, we hypothesized a neural network that made saccades by driving the eyes to an orbital position rather than preprogramming a distance for movement. Computer simulation of this model produced both realistically appearing normal saccades and, when appropriately "lesioned" to simulate a loss of saccadic "burst" neurons in the pontine reticular formation, slow saccades that could be modified in flight.


[Histogenesis of the immune system of the "nude" mouse. IV. The ultrastructure of the thymus anlage in 12 and 13 days old embryos (author's transl)]. The development of the thymus of the heterozygous (nu/+) mouse is indistinguishable from that of "normal" mice (Groscurth and Kistler, 1975). However, previous studies have shown that the thymus anlage of the homozygous (nu/nu) mouse differs significantly from that of its nu/+ counterpart. This morphological deviation becomes detectable by light microscopy during the 13th day post conceptionem (p.c.). It was assumed that, at the ultrastructural level, this maldifferentiation could become manifest at an earlier developmental stage. Therefore, the thymus anlage of 12 and 13 day-old nu/nu and ICR embryos was investigated electron microscopically. The "nude" mice with the genetic background BALB/c were kept under the same conditions as described previously (Groscurth and Kistler, 1975). Mice of the strain ICR were used as controls. Virgin nu/nu females were mated with nu/nu males and the pregnant animals were sacrificed on the 12th of 13th day p. c. The embryos were fixed in 2.5% glutaraldehyde, postfixed in I% OsO4 and embedded in Epon.


A fine structure study of human thymus.

A fine structure study of human thymus. A study of the fine structure of human thymus, including normal hyperplastic and with thymoma, is reported in this paper. There is increasing experimental evidence that thymic epithelial cells are a source of hormone. It is, therefore, of interest that we found epithelial cells containing intravesicular cytoplasmic material that reacted with silver methenamine as do mucoproteins. Similar material, possibly extracellular, was seen in close contact with lymphocytes and macrophages in the thymus. The results suggest a possible mechanism for epithelial cell/lymphocyte interaction. Some epithelial cells also showed phagocytic features and all appear to play a structural role. The presence of nuclear pockets was noted within lymphocyte nuclei.


The watershed: a factor in coronary vein graft occlusion. In 50 patients with one or more aortocoronary saphenous vein grafts investigated by angiography the patency rate of grafts inserted into arteries with a total proximal occlusion was significantly higher than of those inserted into arteries with a proximal stenosis. The interval between operation and investigation in the two groups was similar. In 10 patients with double grafts, one to an occluded and one to a non-occluded artery, there were 7 with one blocked graft, in each case to the non-occluded artery. In the other 3 both grafts were patent. A watershed was shown at angiography in one patient with a graft inserted into a stenosed artery; the distal run-off appeared good, but reflux of the contrast up the coronary artery into the aorta occurred when injecting into the graft, and vice versa. This watershed may operate to a minor degree in all grafts inserted into non-occluded arteries, and by causing stasis at the anastomosis, could explain the higher incidence of graft occlusion in this group. Ligation of the coronary artery proximal to the anastomosis may therefore be necessary to achieve the highest patency rate.


Long-term results of arterial counterpulsation in acute severe cardiac failure complicating myocardial infarction. Thirty patients were discharged from hospital after treatment with arterial counterpulsation for acute severe heart failure complicating myocardial infarction. Seventeen patients had been in cardiogenic shock--13 with power failure alone, and 4 with a mechanical complication which required corrective surgery. Thirteen patients were in impending or 'preshock'. The follow-up period after infarction averaged 13-1 months. Results were good in 'preshock' patients, and in shocked patients with a surgically correctable mechanical complication. Results were poor in shocked patients with power failure alone. Counterpulsation has an important supportive role in the treatment of complicated myocardial infarction, provided that intervention is prompt and mechanical complications, if present, are corrected early.


Esophageal varices in Felty's syndrome: A case report and review of the literature. A case of upper gastrointestinal tract hemorrhage secondary to esophageal varices in a patient with Felty's syndrome prompted a review of the pathogenesis and treatment of this condition. Six previously reported cases of this association were found. The clinical picture is that of long-standing rheumatoid arthritis with severe articular and extraarticular manifestations including splenomegaly, depression of the blood elements, mild liver function abnormalities, portal hypertension without cirrhosis or portal vein obstruction, an elevated splenic blood flow, and a reduction in portal hypertension by simple splenectomy. The presence of portal hypertension with varices may be another indication of splenectomy in patients with Felty's syndrome.


Comprehensive study of humoral and cellular immune abnormalities in 26 patients with systemic amyloidosis. Serum immunoglobulin abnromalities in nonfamilial and systemic primary amyloidosis are distinct from those seen in multiple myeloma and more closely resemble those seen in benign monoclonal gammopathy. Surface lymphocyte characteristics also differentiate amyloid patients with or without monoclonal immunoglobulins from those with malignant B-cell dyscrasias. In vitro lymphocyte transformation with phytohemagglutinin and pokeweed mitogen is normal in amyloidosis, but T-cell function is significantly depressed in both primary and secondary amyloid disease as measured by concanavalin A responses.


Antibody-mediated lymphocytotoxicity in rheumatoid arthritis and systemic lupus erythematosus. Lymphocyte-dependent antibody cytotoxicity (LDAC) was studied using peripheral blood and in some instances synovial fluid cells from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). No difference from normal controls was observed with peripheral blood lymphocytes from either RA or SLE. Marked decrement in LDAC effector cell activity was present particularly with RA synovial fluid cells. Sera from patients with RA or SLE as well as RA synovial fluids markedly inhibited LDAC.


The effect of methotrexate on spontaneous mammary adenocarcinomata in female C3H mice. The effect of methotrexate on solid rodent tumours has been investigated using the spontaneous mammary adenocarcinoma of the female C3H/Bts mouse. As these tumours exhibit a wide range of volume doubling times, calculations of tumour response to methotrexate must be related to doubling time. When methotrexate is injected into the tumour a dose-dependent tumour response is obtained. Systemic citrovorum "rescue" prevents methotrexate lethalities but reduces tumour response by a factor of 2. Methotrexate-treated tumours have an increased volume doubling time post treatment.


Lysosomal acid hydrolases in human lymphocyte subpopulations. Acid phosphatase and beta-glucuronidase activities have been determined cytochemically in T, B and null lymphocytes as part of an effort to charaterize the human haemopoietic stem cell. A combination of weak acid phosphatase activity and strong beta glucuronidase staining, in the form of a single large granule, has been shown to be specific for T cells. On the basis of this approach alone, non-T cells could not be further subclassified. Further cytochemical evaluation is being explored.


Biosynthesis of 3'-deoxyadenosine by Cordyceps militaris. Mechanism of reduction. The biosynthesis of 3'-deoxyadenosine (cordycepin) by Cordyceps militaris has been investigated using [U-14C]adenosine and [3-3H]ribose. Crystallization of the resulting radioactive 3'-deoxyadenosine to a constant specific activity showed incorporation of both labeled compounds. A control showed that the 3H:14C ratio of the AMP isolated from the RNA was the same as the 3H:14C ratio in the 3'-deoxyadenosine. The 14C ratio in the adenine: ribose of the [U-14C]adenosine added to the 3'-deoxyadenosine producing cultures of C. militaris and of the isolated 3'-deoxyadenosine was the same, e.g. 50:50. These data provide strong evidence that adenosine in converted to 3'-deoxyadenosine without hydrolysis of the N-riboside bond. Degradation of the 3-deoxyribose from 3'-deoxyadenosine showed that the 3H was retained on carbon-3. These results suggest that the formation of 3'-deoxyadenosine may proceed by a reductive mechanism similar to that for the formation of 2'-deoxynucleotides.


Circular dichroism of rhodopsins and porphyropsins. Circular dichroism and absorption spectra were determined for digitonin extracts of three rhodopsins: cattle, grass frog, and pigeon; and three porphyropsins: channel catfish, bluegill sunfish, and redear sunfish. A comparison of these spectra shows the following: (1) Porphyropsins, like rhodopsins, exhibit two positive CD peaks in the spectral region 320--700 nm: an alpha peak at about 520 nm and a small beta peak at about 355 nm. These peaks substantially diminish upon bleaching. (2) In the CD spectra the alpha peaks of the porphyropsins are larger than the alpha peaks of the rhodopsins, while the beta peaks are smaller than those of the rhodopsins. This is just the opposite of the corresponding relationship between the peaks in the absorption spectra. (3) The maxima of these peaks in the CD spectra of rhodopsins and porphyropsins are consistently blueshifted from corresponding maxima in absorption spectra. (4) Some of the visual pigments show additional positive CD peaks in the spectral region 250--320 nm. In all the visual pigments studied, the CD spectra in this region decrease on bleaching. No reciprocal relationship is observed between any of the CD bands in the visible and near ultraviolet region of the spectrum.


The rate of rhodopsin phosphorylation in isolated rentinas of frog and cattle. Phosphorylation of rhodopsin has been measured in isolated retinas incubated with 32P-phosphate under physiological conditions. The half-time of the light-induced phosphorylation was found to be approximately 2 min with frog retinas at 21 degrees C, and in the order of 1--2 min with cattle retinas at 36 degrees C. It is suggested by this slow rate that the phosphorylation reaction is not directly involved in the chain of events which lead from absorption of a photon to excitation of the photoreceptor cells but may perhaps have a regulatory function in controlling light/dark adaptation.


Cytidine-5'-monophosphate-N-acetylneuraminic acid. Asialoglycoprotein sialic acid transferase activity in liver and serum of patients with juvenile hepatic cirrhosis and alpha-1-antitrypsin deficiency. The molecular basis for the accumulation of a substance which displays the immunological reactivity of alpha-1-antitrypsin within vesicles of liver parenchymal cells of individuals with hepatic cirrhosis and serum alpha-1-antitrypsin deficiency remains unclear. We recently reported that serum from a patient with alpha-1-antitrypsin deficiency and hepatic cirrhosis was substantially deficient in sialyltransferease (EC 2.4.99.1) an enzyme which transfers sialic acid from cytidine 5'-monophosphate-N-acetylneuraminic acid to a variety of asialoglycoprotein acceptors. In the present report we have extended these studies to include serum from five additional patients with alpha-1-antitrypsin deficiency and juvenile hepatic cirrhosis as well as a liver specimen obtained at autopsy of one of these patients. We find the sialytransferase activity in serum from six patients with alpha-1-antitrypsin deficiency and hepatic cirrhosis to be 50% of healthy pediatric control values and 30% of pediatric patients with liver disease. However, serum from family members homozygous for alpha-1-antitrypsin deficiency but without hepatic cirrhosis, and serum from patients with a variety of other kinds of liver disease, failed to exhibit the marked sialytransferase deficiency. Similar assays carried out on a homogenate of a liver sample from one patient with alpha-1-antitrypsin deficiency and hepatic cirrhosis indicated that the deficiency of sialyltransferase activity was not demonstrable in liver. Furthermore, a comparative kinetic analysis of serum and liver sialytransferase in normal and afflicted individuals failed to detect differences in substrate affinities which might account for a decrease in functional sialyltransferase capacity in individuals with alpha-1-antitrypsin deficiency and hepatic cirrhosis. These observations suggest that the serum sialyltransferase deficiency in such patients probably arises after chronic and extensive liver disease involving hepatic accumulation of alpha-1-antitrypsin rather than the enzyme deficiency being the primary cause of the hepatic cirrhosis and alpha-1-antitrypsin deficiency.


Inhibition of urokinase by complex formation with human alpha1-antitrypsin. Human alpha1-antitrypsin was prepared from fresh human plasma by (NH4)-SO4-precipitation, gel filtration, affinity chromatography on concanavalin A, ion exchange chromatography and isotachophoresis. Human urokinase (EC 3.4.99.26) (plasminogen activator from urine) with M, 46 000 and 36 000 was further purified from Urokinase Leo reagent preparation by gel filtration on Sephadex G-100 Superfine. The hydrolytic activity of urokinase on acetyl-glycyl-L-lysine methyl ester acetate (Ac-Gly-Lys-OMeAc) was inhibited in a strong time-dependent manner by alpha1-antitrypsin. Complex formation between enzyme and inhibitor could be demonstrated in crossed immunoelectrophoresis against anti-alpha1-antitrypsin and anti-urokinase serum as well as by sodium dodecyl sulphate polyacrylamide gel electrophoresis. The latter method revealed the formation of 1:1 and 2:1 molar enzyme-inhibitor complexes.


The type, amount, location, and energy transfer properties of the carotenoid in reaction centers from Rhodopseudomonas sphaeroides. Analysis of photosynthetic reaction centers from Rhodopseudomonas sphaeroides strains 2.4.1 and Ga shows that each contains approx. 1 mol of a specific carotenoid per mol of reaction center. In strain 2.4.1. the carotenoid is spheroidene (1-methoxy-3,4-didehydro-1,2,7',8',-tetrahydro-psi,psi-carotene); in strain Ga, it is chloroxanthin (1-hydroxy-1, 2, 7', 8'-tetrahydro-psi,psi-carotene). The carotenoid is bound to the same pair of proteins as are the bacteriochlorophylls and bacteriopheophytins of the reaction center. This binding induces strong circular dichroism in the absorption bands of the carotenoid. The carotenoid is close enough to the other pigments of the reaction center so that light energy transfers efficiently from the carotenoid to the bacteriochlorophyll, sensitizing bacteriochlorophyll fluorescence. The fluorescence polarization spectrum of the reaction centers shows that the transition vectors for the visible absorption bands of the carotenoid lie approximately parallel to the 600 nm (Qx) transition of the bacteriochlorophyll complex.


Investigation of peptide-nucleotide interactions using template chromatography. The specific recognition of peptide sequences by oligodeoxy adenylic acids. Polyvinylalcohol has been substituted with oligodeoxyadenylic acid and the resulting polyanion polyvinyl (pA)n irreversibly attached to DEAE-cellulose. Peptide-oligonucleotide interactions have been studied using a column chromatographic technique with the polyvinyl (pA)n-DEAE-cellulose as a stationary phase.


Antinuclear factor-positive mental depression: a single disease entity? Antinuclear factor (ANF) was present in the serum of about 30% of 53 patients newly admitted to the psychiatric hospital because of mental depression. Clinically, ANF-positive depression closely resembles manic-depressive psychosis but tends to be more resistant to treatment. It is suggested that ANF-positive depression may be a quite distinctive disease.


Electrophoretic mobility of blood lymphocytes in cancer patients. Determination of electrophoretic mobility of lymphocytes in 70 cancer patients shows a significant decrease of the fast moving cells. It seems to be a relation between the percentage or absolute number of the rapid lymphocytes and dissemination and prognosis of the disease. This decrease is in agreement with the variations of the T lymphocyte population described in cancer patients with other methods. On the contrary, although there is reduction of total blood lymphocytes, the number of slow moving cells is not reduced. The changes observed in mean migration speed of fast and slow migrating lymphocytes could indicate more selective alterations in some cell subpopulations.


Formation of mouse red cell rosettes by "hairy" cells. Rosette formation with mouse red cells was observed in the "hairy" cells of four cases of leukaemic reticuloendotheliosis. A similar observation was made on B-lymphocytes from chronic lymphoid leukaemia but the monocytes in monocytoid leukaemia did not form rosettes. This finding provides new evidence for the B-cell nature of the "hairy" cell.


Ultrastructural abnormalities of the chondrocytes of the growth cartilage of a type of poly-epiphyseal dysplasia with a probable autosomal recessive transmission. In two cases of polyepiphyseal dysplasia with a probable autosomal recessive transmission, ultrastructural abnormalities were found in the chondrocytes of the tibial epiphyseal growth plate. The largest part of the chondrocytes is occupied by many large vacuoles. They are bounded by a single membrane and have an electron-lucent background in which electron-opaque granules and delicate spiral filaments are visible. The ultrastructural abnormalities suggest a storage disorder probably limited to the chondrocytes.


[Effect of thymocyte autotransplantation on postradiation regeneration of hematopoiesis]. Experiments were conducted on Wistar rats irradiated in a dose of 400 R; a study was made of the effect of thymocyte autotransplantation (4-10(8)--8-10(8)) on the restoration of cell number of the bone marrow and the spleen. There was revealed a significant stimulating effect of autotransplantation of thymocytes on the erythroid and granulocytic series in the bone marrow and on the lymphoid one in the spleen during the restoration (the 5 th-- 7 th days) after the irradiation. Irradiation of the thymocyte suspension with gamma-rays in a dose of 10 000 R failed to prevent the effect of autotransplantation on the bone marrow, but decreased its stimulating effect. A conclusion was drawn on the interaction of the administered thymocytes with the stem hemopoietic cell.


[Hyperpolarization of frog skin exposed to furosemide]. When applied only to the outer surface of the isolated frog skin furosemide caused a prompt, dose-related (0.1--1.0 mg/ml) and fully reversible increase in potential difference; it did not change the short-circuit current, however. Potential differences were not altered by furosemide in the Ringer-sulphate solution. Furosemide-induced increase of potential differences could be reversed by nystatine which increased the ionic permeability. These results suggest that furosemide could decrease the passive entrance of chlorides through the barrier of the apical cell membrane of the frog skin.


[Aggregate-hemagglutination test for anti-erythrocyte antibodies]. A new test for detection of antierythrocyte antibodies is described; one of its variants is three orders of magnitude more sensitive than the classic Coombs test. The proposed procedures are based on the agglutination of the red blood cells following addition of test-erythrocytes coated with the aggregated proteins of an antiglobulin serum. Results of application of the technique for diagnosis of the autoimmune hemolytic anemia showed its high specificity and the absence of prozone phenomenon.


[Cytotoxic effect of lymphotoxin on a culture of macrophages]. Results of study of the cytotoxic effect of the lymphotoxin on the monolayer culture of the peritoneal macrophages used as target cells are presented. The lymphotoxin was obtained following an 18-hour incubation of the lymph node cells of guinea pigs with delayed hypersensitivity to tuberculoproteins, in the presence of the specific antigen (tuberculin). It was shown that only on the 5th--6th day of cultivation did the supernatants destroy more than half of the macrophages in 70% of the experiments. The death of the macrophages during the later periods of cultivation, in comparing with the L-cells, suggests a different resistance of these target-cells to the cytotoxic effect of the lymphotoxin.


Granulopoiesis in severe congenital neutropenia. The pathogenesis of the granulopoietic failure in three children with severe congenital neutropenia was studied. Mature neutrophils were absent from both peripheral blood and bone marrow. Assay of bone marrow granulocyte colony-forming cells (CFU-C) in a methylcellulose tissue culture system using colony-stimulating activity (CSA) from peripheral blood leukocytes demonstrated normal or increased concentrations of CFU-C compared to those from marrows of 60 age-matched controls. Colonies were of normal size and by light microscopy appeared to contain granulocytes in all stages of maturation including the mature polymorphonuclear neutrophil. CFU-C from peripheral blood of two patients were normal. Production and activity of CSA from the patients' peripheral blood leukocytes and urinary CSA excretion were normal. No serum inhibitors against CFU-C or CSA could be demonstrated using both control and autologous marrow. The defect did not appear to be due to a lack of granulocytic stem cells, a reduction of humoral stimulators of granulopoiesis, nor the presence of an inhibitor as measured by these techniques.


Decrease and altered distribution of human T antigen on chronic lymphatic leukemia cells of T type, suggesting a clonal origin. B- and T-cell markers were studied in a patient with chronic lymphocytic leukemia and erythroderma. The absence of immunoglobulin, complement receptor, and Fc receptor, and the presence of sheep erythrocyte receptor and T-cell antigen on the membrane of the leukemic cells classified them as thymus derived. Using quantitative microphotometric immunoautoradiography, surface antigen densities were measured at the cellular level with the following results: (1) The density of T-antigenic sites was less on leukemic cells compared to normal T lymphocytes. (2) The T-antigen densities of leukemic lymphocytes varied less from cell to cell forming a homogeneous peak in histograms. (3) An Ig density of normal B lymphocytes was demonstrated on the residual T-antigen-negative cells. The results were qualitatively confirmed by direct immunofluorescence and electron microscopy with peroxidase-labeled antibodies. Furthermore, the surface antigens were quantitative microcomplement fixation test which revealed reduced binding of anti-T-cell antibodies and complement, and no antiglobulin fixation on the leukemic lymphocytes. Since lymphocytes with normal T-antigen concentration could not be found among the leukemic T lymphocytes, a lack of normal T cells was assumed. The findings that there was a decrease and altered distribution of surface markers on chronic lymphatic leukemia cells of the B- and T-cell type are discussed as further arguments referring to their clonal origin.


Colony-stimulating factor in patients with chronic neutropenia. Urinary and serum colony-stimulating factor (CSF) levels were measured in 11 patients with chronic idiopathic neutropenia without infections and in 10 normal individuals. Urinary CSF output was determined using mouse marrow target cells, and serum CSF activity was assayed with human marrow target cells by the double agar layer technique. Using these methods, there was no significant difference between CSF levels of neutropenic and normal subjects. These data indicate that CSF levels are not inversely related to the blood neutrophil count in chronic idiopathic neutropenia and suggest that CSF is not a hormone regulating the blood neutrophil count in a manner analogous to the erythropoietin regulation of circulating erythrocyte levels.


[Fc receptors and surface immunoglobulins in cells of hairy cell leukemia]. Using 125I-labelled aggregated IgG in a quantitative assay a strong expression of Fc-receptors was found on the leukemic cells of a patient with hairy cell leukemia. The Fc-receptor activity on these cells was much higher than that on monocytes and B-lymphocytes from normal blood. Surface immunoglobulins were detected by radioautography using radioactively labelled (Fab')2-fragments of monospecific antibodies directed against immunoglobulin heavy chains. Prior to radioautography the cells were stained for the tartrate resistant acid phosphatase. It was found that all cells containing this enzyme bore sigma-chains on their surface. On more than 90% of these cells a simultaneous expression of mu-chains was detected. gamma-Chains could only be demonstrated on cells which were negative for the tartrate resistant acid phosphatase; part of these cells, however, were hairy cells by morphological criteria.


[Anti-immunoglobulins in multiple myeloma and benign monoclonal hyperglobulinemia]. Sera from 50 healthy adults, from 21 patients with multiple myeloma (MM) and from 11 patients with benign monoclonal hyperglobulinaemia (BMH) and from 28 patients with sarcoidosis were examined for the presence of anti-IgG-activity by passive haemagglutination technique. 62% of healthy adults (titre less than 2) and all of the sera from patients with MM and BMH (titres 32-512) as well as 42% of the sera from sarcoidosis patients were found to be anti-IgG positive. The anti-IgG positive sera showed also anti-(Fab)2-activity (with the exeption of 2 sera from sarcoidosis patients). No significant differences could be found between anti-Ig activity in sera from MM patients with BMH. There was also seen no correlation of anti-Ig with the clinical course of the disease. After column chromatography we could detect the partially simultaneous presence of anti-Ig with anti-Fc-specificity (MW ca. 900,000) and with (Fab)2-specificity (MW 150,000 or less than 90,000). Antibody dependent cytotoxicity (using melanoma cell lines as targets) was significantly inhibited by the isolated anti-Ig-fractions with low molecular sizes (MW less than 90,000). From these results it seems possible that anti-immunoglobulins may play a role in the clinical course of the disease.


[Colony-stimulating activity in urine and serum in a child with cyclic neutropenia]. Colony stimulating activity (CSA) was estimated in daily urine samples and weekly plasma specimens of a 4-year-old girl with familial cyclic neutropenia. Nadirs of neutrophils and peaks of monocytes were found in regular cycles of 28 days. A close correlation was observed between nadirs of neutrophils and peaks of blood monocytes and colony stimulating activity in the urine. The role of colony stimulating factor as regulatory factor in granulopoiesis in cyclic neutropenia is discussed.


[Effect of cordycepine on cultured chicken fibroblasts]. Cordycepin strongly inhibits cell multiplication in chick fibroblasts cultivated in vitro. Many cells cannot enter into mitosis and cell separation at telophase is disturbed. However, DNA synthesis takes place. Nucleolar alterations observed in the treated cells are probably responsible for some of these effects.


Isotonic and isometric responses of different tonic muscles to agonists and antagonists. 1 With isotonic recording the percentage of muscle shortening as compared with the maximal possible shortening, and with isometric recording the percentage of developed tension were determined. In relatively 'thick' muscles, such as dorsal leech muscle, frog rectus abdominis or protractor pharynx of holothuria (0.3-0.8 mm thick), the concentrations of a full agonist (carbachol) producing a given percentage of tension, (e.g. 50%) are about 5 times greater than the concentrations, producing the same percentage of shortening. In 'thin' muscles the difference between the percentage of shortening and tension is either small (retractor dentis of the sea urchin, 0.1 mm thick, response to carbachol) or absent (guinea-pig ileum, 0.06 mm thick, responses to methylfurmethide). The possible mechanism underlying this difference is discussed. 2 With partial agonists (dodecamethonium and heptamethonium) the fractional tension of the frog rectus abdominis is always less than the fractional shortening and the correlation between shortening and tension is the same as in the case of full agonists. 3 The blocking activity of (+)-tubocurarine on the frog rectus abdominis is the same in isotonic and in isometric conditions. 4 On the frog rectus abdominis the alkylating agent, decamethonium mustard, does not produce any 'parallel shift' of the dose-response curve for carbachol, the only result of alkylation being a decrease in maximal response, which is more pronounced in isometric than in isotonic conditions. The degree of decrease is in accordance with the correlation between percentage of shortening and percentage of tension in the absence of alkylating agent. Probably this muscle does not possess any 'spare receptors'. 5 On the frog muscle the dose-isometric response curve for acetylcholine (ACh) is shifted toward greater concentration about 33-fold as compared with the dose-isotonic response curve but after the inhibition of cholinesterases the shift is only about 6-fold. The same shift (5-fold) is observed for carbachol, which is not hydrolysed by cholinesterases. The results with ACh are due to the fact, that after cholinesterase inhibition the sensitivity to ACh increases in isotonic conditions only 13-fold, but in isometric conditions it increases 71-fold. Probably under isometric conditions, when the muscle remains in the extended state, the rate of hydrolysis of ACh is much greater than under isotonic conditions when the muscle is shortened during contraction.


Fetal complications of obstetric cholestasis. Among 56 pregnancies complicated by obstetric cholestasis five intrauterine deaths and one neonatal death occurred between 33 and 39 weeks, and a further six infants required urgent delivery for intrapartum asphyxia. Eighteen spontaneous premature deliveries occurred. Five mothers required specific treatment for unexplained postpartum haemorrhage. Cholestasis of pregnancy is therefore not a condition benign to the fetus, and it may contribute to increased maternal morbidity.