A comparison of circling models for the detection of antiparkinson activity. Apomorphine, d-amphetamine, methylphenidate, nomifensine, ET495 and amantadine each induced a dose-dependent stereotyped behaviour in the rat. L-Dopa was inactive in the absence of any pretreatment. The behaviour induced by apomorphine, methylphenidate, nomifensine and amantadine persisted following pretreatment with a-methylparatyrosine. However, only the effect of apomorphine developed following combined pretreatment with reserpine/a-methylparatyrosine. The effects of all stereotypic agents were inhibited by haloperidol, apomorphine, methylphenidate and nomifensine being most resistant. All agents, including L-Dopa, induced a dose-dependent contralateral circling behaviour in animals with asymmetric lesion of the medial raphé nucleus and a dose-dependent ipsilateral circling after unilateral lesion of the substantia nigra. Following unilateral lesions in the ventromedial area of the medial forebrain bundle (medial to the substantia nigra and carrying 5-hydroxytryptamine neurones) amphetamine caused an ipsilateral circling behaviour, amantadine a behaviour which was characterised by definite bursts in either direction, and all other agents caused contralateral circling.


Propranolol in the treatment of opiate dependence -- a controlled study. Two doublebling placebo controlled experiments designed to elucidate the alleged narcotic blocking effect of propranolol wer performed. In the first experiment, propranolol 40 mg or 20 mg was given together with methadone during the acute withdrawal phase of opiate addiction. The second experiment assessed whether 10 mg of propranolol, given 2 hrs before 30 mg of morphine i.v., reduced the euphoric effects of the latter drug. In none of the experiments could narcotic blocking effects be detected. The group receiving 40 mg propranolol during detoxification exhibited the highest proportion of patients staying for the whole prescribed detoxification period.


[View of the past: Roentgenography of an Egyptian mummy]. Report concerning roentgenographic examinations of an Egyptian mummy dating back to 900 B.C. from the "Museum für Völkerkunde Freiburg/Breisgau". The study was performed to detect funeral gifts which can be found otherwise only if the linnen bandage of the mummy is destroyed. Extraordinary findings were degenerative osteoarthritis of the spine and joints, pseudo-gout, marked caries of several teeth and signs for a healed occipital osteomyelitis. Suggestions are discussed about a particular compression of thorax and pelvis which is apparently due to the technique of bandaging. This was not observed in examinations of other mummies. Fractures of the first to third phalanges suggest forceful removal of precious rings. A circular-shaped opening in the parietal bone and a small radiodense foreign body which projects over the pharynx remain unexplained.


Alcohol and affect in dyadic social interaction. The effects of alcohol on emotional behavior during social interaction were studied in an experiment utilizing unstructured discussions between male-female couples. All subjects participated in an alcohol (1.0 ml/kg) and placebo session, and a small number took part in a third higher dose session (1.5 ml/kg). Quantitative and qualitative ratings of affect were made from the recorded interactions. Alcohol produced significant increases in the affects of elation--giddiness and happiness--and an overall increase in total emotional expression. Only some aspects of anxiety were affected by alcohol. Hostility and aggressiveness were not increased on two quantitative measures but showed a significant increase on qualitative scores in the low dose session. Although there was no consistent relationship between blood alcohol level and emotional response , drinking history significantly altered emotional response to alcohol (tolerance effects). The euphoric effects of alcohol that we found are discussed in terms of the unique aspects of the experimental situation employed. Some important variable are delineated that may influence responses to alcohol.


The effects of plumbous ion on protein biosynthesis in reticulocytes. Plumbous ion a potent inhibitor of hemoglobin synthesis by reticulocytes in vivo, is not as effective in inhibiting in vitro globin synthesizing systems prepared from these cells. The reticulocyte is considerably more sensitive to Pb2+ than are leukemic leukocytes, HeLa cells or bacteria. In fact, protein synthesis in leukemic leukocytes is actually stimulated by Pb2+. The synthesis of non-heme protein as well as hemoglobin is inhibited by Pb2+ in reticulocytes and the synthesis of alpha chains is inhibited to a greater degree tcids into reticulocytes. All of these observations are consistent with the biosynthesis of heme rather than any of the steps in protein biosynthesis being the locus for inhibition of hemoglobin synthesis by low levels of plumbous ion. Also, there is marked biological variations in the susceptibilities of reticulocytes from different rabbits to Pb2+.


Comparison of two steroid preparations used to treat tennis elbow, using the hypospray. Methyl prednisolone acetate and hydrocortisone acetate were compared in a trial using the Hypospray to treat tennis elbow. There was little difference between the two preparations as far as side-effects and short-term suppression of symptoms were concerned, both being successful. However, late recurrence was very common in both groups, suggesting that a reappraisal of local steroid in this condition is needed.


A comparison of stable and 3H- labelled polyethylene glycol 4000 as non-absorbable water phase markers in the human ileum and faeces. Polyethylene glycol  4000 (PEG plus 3H-PEG) was used as volume indicator during ileal perfusion in man. Faeces, urine, ileal infusates, and aspirates were investigated. Turbidimetrical assay and liquid scintillation counting (in the faeces radioassay was done after conbustion) yielded similar estimates of water absorption and secretion. Tracer amounts of 3H were found in the urine, indicating a minimal absorption. The simplicity of 3H radioassay and the reliability of 3H-PEG as a non-absorbable water phase marker is emphasized.


Studies of gastrointestinal interactions. VII. Characteristics of the absorption pattern of sugar, fat and protein from composite meals in man. A quantitative study. The absorption of sugar, fat, and protein after feeding two meals, differing in their content of glucose, was investigated in 7 healthy subjects, in double experiments with the multiple indicator dilution method. An average of 75% of the emptied amounts of sugar and 80% of the emptied fat and protein was absorbed during transit of the proximal 70 cm of the intestine. Differences in the absorption pattern between the meals were recorded, resulting from their different intragastric behaviour and gastric emptying pattern. Within the first hour significantly higher amounts of fat and protein were absorbed after the glucose-free than after the glucose-containing meal, whereas from the latter most of the glucose was absorbed early after ingestion. The absorptive capacity of the investigated segment was not exceeded for any component of the meals, owing to compensatory mechanisms by which the gastric emptying rate was inhibited and the transit time through the segment prolonged. The efficiency of sugar absorption was related to the transit time through the segment, in that a constant fraction was eliminated from the intestinal lumen per minute increase of the mean transit time. The net endogenous contribution of protein and fat at the exit of the segment amounted to an average of 3.0 g protein and 1.2 g fat during 3 hours.


In vitro pathogenetic studies of coeliac disease. Effects of protein digests on coeliac intestinal biopsy specimens maintained in culture for 48 hours. Jos, J., Lenoir, G., de Ritis, G. & Rey, J. In vitro pathogenetic studies of coeliac disease. Effects of protein digests on coeliac intestinal biopsy specimens maintained in culture for 48 hours. Scand. J. Gastroent. 1975, 10, 121-128. Intestinal biopsies from controls and from children with treated or untreated coeliac disease were cultured for 48 hours in the presence or absence of various peptic-tryptic (P.T.) or peptic-tryptic-chymotryptic (P.T.C.) digests of gliadin and casein, using a modified organ culture method. In flat biopsy specimens obtained from children with active coeliac disease and maintained in culture in the presence of P.T. or P.T.C. digests of gliadin, whether autoclaved or not, a cytotoxic effect was obvious; but this effect was in part unspecific, since P.T. digests of casein were also slightly noxious in such experimental conditions. Biopsies from controls or from children with coeliac disease in remission were not affected by the presence in culture medium of casein or gliadin digests, whereas coeliac biopsies, also obtained from patients in remission but after gluten challenge, were specifically injured during culture with gliadin peptides. On the other hand, a thorough P.T.C. hydrolysis of gliadin abolished all its in vitro noxious effects, suggesting that its toxicity is related to a relatively large peptide.


Acetylsalicylic acid and gastrointestinal bleeding measurement of blood loss using a modified radioactive chromium method. A comparative study of the gastrointestinal blood loss during intake of a new buffered acetylsalicylic acid (ASA) preparation and plain ASA tablets has been performed. A modified radioactive chromium method was used. The 51Cr activity was considerably less than that used in previous methods, and no feces homogenization was necessary. The study was performed in 18 volunteers using a randomized crossover design. A significant reduction in gastrointestinal bleeding was registered during ingestion of the buffered ASA in comparison with the plain ASA tablets.


Effects of 13-nle-motilin in man--inhibition of gastric evacuation and stimulation of pepsin secretion. In 3 healthy male volunteers, graded doses of 13-norleucine-motilin (13-nle-motilin)--synthetic analogue of motilin and biologically equivalent to the natural polypeptide--were given intravenously on separate days. Gastric emptying, as determined by means of a radioisotope method, was slowed down dose-dependently by increasing doses of 13-nle-motilin. This was indicated by increasing "half-lives" and "starting indices" of the gastric emptying process, and by decreasing pyloric loss rates, respectively. The gastric pepsin output rose markedly from the basal level during intravenous infusion of 13-nle-motilin.


Gastric secretory inhibition by two 16-methylated analogs of prostaglandin E2 given intragastrically to patients with duodenal ulcer disease. The effects of two methylated analogs of prostaglandin E2 (PGE2), namely 16,16-dimethyl PGE2 and its methyl ester, on gastric acid and pepsin secretion have been studied in 5 ulcer patients. Both analogs produced significant inhibition of acid secretion in a dose-dependent fashion, but the effect was less pronounced than the inhibition found in a group of healthy volunteers, and it was necessary to give 140 mug of each analog to reach about the ED50. The mean values of pepsin output and pepsin concentration were decreased following administration of PGE2, but the individual results varied.


Needle-like crystals in plasma cells in a patient with a plasma cell proliferative disorder. A patient with a plasma cell proliferative disorder and a monoclonal IgG-kappa protein in the serum was observed over a period of four years. Two unusual features were seen in this patient: (1) An apparently benign course in spite of relatively large and slowly increasing amounts of Bence Jones protein (monoclonal kappa light chains) in the urine, and (2) crystalline structures located outside the cisternae of the endoplasmic reticulum in a large number of bone marrow plasma cells. The crystals, which ultrastructurally appeared to be composed of protein material, were not stained by immunofluorescent antisera to immunoglobulins. They were, however, observed only in cells staining for gamma heavy and kappa light chains. This suggest an association between the crystalline structures and the synthesis of monoclonal immunoglobulin proteins.


[Treatment of psoriasis with an orally administered effective new vitamin A acid derivative. Preliminary report]. The retinoic acid derivative Ro 10-9359 has been tested in 24 patients with psoriasis. In all patients the therapeutic activity was good to excellent. The symptoms of the hypervitaminosis A syndrome were slight to marked. The ratio between the therapeutic effectiveness and the side effects was favourable only in cases with severe psoriasis.


[Leukocyte transfusion. An overview].

[Leukocyte transfusion. An overview]. Today the increased risk of infection in patients with transient severe neutropenia can be reduced effectively by three different approaches:1.gnotobiotic patient isolation with whole body decontamination by non-resorbable antibiotics;2. treatment of documented or suspected infection with a conbination of bactericidal antibiotics and/or antimycotics; 3. granulocyte transfusions in the case of life-threatening antibiotic-resistant infections. This third therapeutic approach against severe resistant infection is proving increasingly effective and cannot at present be replaced by different therapeutic measures. The efficiency of granulocyte transfusions depends on: 1. substitution of at least 1 X 10-10 granulocytes per transfusions; 2. repeated transfusions of granulocytes within several consecutive days in the event of only partial success; 3. the transfused granulocytes should not be immediately destroyed in the recipient by preformed antibodies, a factor which makes donor-recipient selection a vital part of the granulocyte replacement program. Severe complications of granulocyte transfusion can be minimized by slow application of the transfused cells. The required number of at least 1 X 10-10 granulocytes for effective transfusion can be collected without significant risk from healthy donors by means of either the "continuous flow centrifuge" (CFC) or the technique of "filtration leukapheresis' (FL). Filtration leukapheresis offers the advantage of a simple collection procedure and much lower cost, coupled with the same numerical and functional effectiveness of cell collection and therapeutic results. Since after transfusion vital granulocytes accumulate in the marginal neutrophil pool, recording of the "post-transfusion increment" is not an accurate parameter of transfusion effectiveness. There is marked accumulation of transfused granulocytes in areas of infection.


Disorders of hemostatic function in patients with systemic lupus erythematosus. A wide spectrum of hemostatic abnormalities is found in patients with SLE. Thrombocytopenia and qualitative platelet disorder (impaired aggregation to collagen) are probably both due to antiplatelet antibodies, which can be found in most patients with the disease. About 10% of patients with SLE have a circulating anticoagulant. These circulating anticoagulants are broadly heterogeneous. Although most reported cases act at the level of the prothrombin converting complex, 15 of the 74 cases here reviewed had other points of action. The anticoagulants are probably all antibodies; they differ (with rare exceptions) from other naturally occurring circulating anticoagulants in having an immediate rather than a progressive effect, and in acting, not against pre-existing procoagulants, but against unstable complexes. An anticoagulant of the type found in SLE is only rarely observed in the absence of SLE; its presence in a patient is thus of some diagnostic importance. Hypoprothrombinemia is a common second lesion in patients with circulating anticoagulants. Its pathogenesis is obscure. Two patients with acquired von Willebrand's disease have been observed. All the hemostatic abnormalities found in SLE probably have immunologic bases; all respond to glucocorticoid treatment.


Recent observations on central nervous system lupus erythematosus. The recent literature on CNS-SLE has been reviewed. An improved prognosis is noted that is thought to be due to the use of high-dose corticosteroids. The frequencies of the various neurologic and psychiatric findings are discussed, and a distinction is noted between organic psychoses and functional psychiatric complaints. The question of corticosteroids versus cerebral vasculitis as the cause of the neuropsychiatric symptomatology in SLE is examined, and the necessity of clear psychiatric diagnosis and treatment is stressed. Recent observations on HL-A antigens, complement, immunoglobulins, virus, and immunocomplexes suggest that the latter are prominent in CNS-SLE, but that an infectious agent may be etiologic in the genesis of SLE. Fifty-four patients not previously reported are discussed. Thirty-eight of them had neuropsychiatric manifestations. The treatment of CNS-SLE with cytotoxic agents, in addition to corticosteroids, is considered, and the experience of the authors with such treatment is presented.


The surface chemistry of bone mineral and related calcium phosphates. A review of the surface chemistry of bone mineral, hydroxyapatite and amorphous calcium phosphate is presented. Small-angle x-ray scattering and low-temperature nitrogen adsorption measurements show the magnitude of bone mineral surface to range from 100-200 m-2/g; the synthetic hydroxyapatite surface can vary from 25-200 m-2/g, while synthetic amorphous calcium phosphate ranges in surface from 20-60 m-2/g, according to the respective preparation conditions. The magnitude of heats of adsorption of certain small molecules (CO, Ar, N2, H2O, CH3OH) on bone mineral and hydroxyapatite show that these are polarizing surfaces that form strong bonds with polar or polarizable molecules; water is hydrogen-bonded to these surfaces with energies ranging from 23 kcal/mole for low coverage to 11 kcal/mole after two full monolayers; concomitantly, methanol ranges from 24 kcal/mole to 9 kcal/mole after the adsorption of one and a half monolayers. Stearic acid will close-pack perpendicularly on bone apatite surfaces when adsorbed from cyclohexane solution in a way reminiscent of the adsorption of this long, straight-chain molecule on water surface. It is believed that these molecules are hydrogen-bonded to electronegative ions on the apatite surface. Synthetic hydroxyapatite has long been used in chromatographic adsorption columns because of the specific bonding capacity the surfaces have for certain proteins and polynucleotides. The metabolic interrelationship of bone mineral and the body fluids is in great part dependent upon the nature and magnitude of mineral surface. From the surface studies described herein it was suggested that a chemical linkage could exist in bone between the mineral surface and certain free polar groups of collagen.


Primary peritonitis in adults.

Primary peritonitis in adults. Infection within the peritoneal cavity without an identifiable source of contamination is rare. The diagnosis is one of exclusion, and can be made with certainty only after a thorough laparotomy. The response to antibiotic therapy is usually prompt and gratifying.


Surgical treatment for nonunion of the scaphoid. Fracture of the scaphoid is the most common injury of the carpal bones. Most scaphoid fractures heal after immobilization. When the fracture does not unite, degenerative arthritic changes and disability may occur. Twenty-four symptomatic nonunions treated surgically were reviewed. Based on presence of union, percent of normal motion, and patients' symptoms, results were rated good in 19 cases and fair in five. Nine of ten patients treated with bone grafting and styloidectomy had union of fractures with good results. All five patients with bone grafting and internal fixation had union. Excision of proximal fragments of more than one third to one half of the scaphoid, and internal fixation alone, had unsatisfactory results. A styloidectomy should excise approximately one half of the radius articulating with the scaphoid. If not enough styloid is excised, osteophytic overgrowth will occur; if too much is excised, the carpus will sublux radially.


Thalamotomy for psychopathic behavior.

Thalamotomy for psychopathic behavior. Six patients characterized by psychopathic behavior were treated with lesions placed in the center median nucleus of the thalamus. There was marked improvement of the psychopathic behavior in five patients. One patient with unilateral thalamotomy was parqially improved. Four of the six patients have been productive and earn a living. The other two have been partially productive. There were no long-lasting postoperative complications after thalamotomy for psychopathic behavior. The various and hyperirritability, and previously have been collectively identified as the "hyperresponsive syndrome". The psychopathic behavior in these condition of the diencephalon.


Liver disease, phlegmonous colitis, and gram-negative sepsis. Phlegmonous colitis, regarded as a terminal event in serious liver disease and hepatic coma, can also occur in reversible liver disease and can be the source of gram-negative sepsis. This paper presented such a case. Improved management of serious liver disease and hepatic coma should include consideration of colonic inflammation as another site of infection that must be treated to avoid complications of sepsis or peritonitis. Abdominal pain and loose or diarrheal stools should arouse a suspicion of the presence of phlegmonous colitis, and should be an indication for treating it and preventing sepsis.


Immunofluorescent study of thyroglobulin during development of embryonic thyroid gland function. The synthesis of the protein component of thyroglobulin was studies by the method of immunofluorescence in the thyroid glands of rat, guinea pig, chicken, and calf embryos. Diffuse specific fluorescence of the cytoplasm was observed in the prefollicular stage of thyroid gland differentiation. It was assumed that the specific fluorescence is due to low molecular weight precursors of thyroglobulin. During the formation of the follicles specific fluorescence is found at the apical poles of the cells and later it is concentrated at the cell-colloid boundary and in the follicular cavity. In calf fetuses in the second half of embryonic development specific fluorescence is observed in addition in the cytoplasm of the follicular cells.


Differentiation of Klebsiella-Enterobacter-Serratia organisms. Differentiation of 625 stains of bacteria which fulfilled the requirements laid down for the definition of the tribe Klebsielleae was carried out using 6 biochemical tests. Five hundred and forty-six strains were identified as members of the genus Klebsiella, 46 of the genus Enterobacter and 33 of the genus Serratia.


Injuries to the skin of the male external genitalia in Southern Africa. The more common injuries to the skin of the male external genital organs are described; some of these mutilations are unique to the African continent. The extent of trauma ranges from small penile skin defects after circumcision to complete avulsion of the skin of the penis and scrotum. The techniques of reconstruction are described.


The prevention of postoperative deep vein thrombosis. Numerous recent reports have appeared dealing with the prevention of postoperative deep vein thrombosis. Simple mechanical measures are inadequate, electrical stimulation has complications, but  the motorised foot mover and pneumatic compression appear effective. Drugs such as coumadin, aspirin and dipyridamole are ineffective, but dextran and sodium pentosan polysulphate appear to have a place. However, if the efficacy and safety of low-dose subcutaneous heparin is statistically confirmed in a multicentre trial, it may lead to the elimination of the morbidity and mortality of postoperative thrombo-embolism.


Analgesic studies in osteo-arthritis.

Analgesic studies in osteo-arthritis. Two studies on a total of 45 patients with chronic osteoarthritis using fenoprofen calcium are presented. Different methods using only subjective criteria (pain intensity scores and pain relief scores) are applied. Measurable analgesic qualities were demonstrated for fenoprofen, which is seen as a valuable addition to the drug therapy of osteo-arthritis.


Candid albicans associated with the gastrointestinal tract of the common pigeon (Columbia livia). Candida albicans was cultured from the upper gastrointestinal tract of 44% and from the lower alimentary tract in 6% of 50 common pigeons (Columba livia). Thirty per cent of samples of pigeon droppings collected from different locations were positive for the yeast. The colony forming units for positive samples ranged from 2 times 10-2-2-8times 10-6 per g dry feces. The percentage of antigenic Groups A and B for the strains of C. albicans isolated was approximately the same as for strains isolated from human sources.


Growth curves of the yeast-like form of Paracocidioides bradiliensis. Growth curves of the yeast-like form of 4 strains of Paracoccidioides brasiliensis based on colony counts on GGY agar and on cell counts weree made. Mean generation times wer 17, 13 and 21 h. for 3 of the strains. The kinetics of growth for all strains showed that dead cells were present in approximately the same proportion as living cells in the initial inocula and their number increased through the exponential phase of growth at a similar rate as that of living cells. Viability counts made in 2-week old cultures of all strains were negative. It is suggested that during growth P. brasiliensis continuously diffuses a metabolite which is lethal to the fungus. Strains of Blastomyces dermatitidis and Histoplasma capsulatum were also sensitive to this lethal effects.


Isolation of keratinophilic fungi from soil in Pavia, Italy. The examination of keratinophilic fungi in 125 soil samples collected in Pavia, Italy revealed the following organism: Microsporum gypseum 23, M. vanbreuseghemii 4, Arthroderma uncinatum 4, Ctenomyces serratus 5, Chrysosporium tropicum 5, unidentified gymnoascacean 1. Arthroderma uncinatum, M. gypseum, M. vanbreuseghemii were isolated from a city park and cultivated soils; C. tropicum, Ct. serratus and an unidentified gymnoascacean were found only in soils from natural woods. The distribution of the different species is discussed.


The action of miconazole of the growth of Candida albicans. The growth of Candida albicans was studied in control cultures and in the presence of miconazole or clotrimazole. Each drug prolonged the lag phase and reduced the total final population. Although miconazole, at the low concentrations used, was a less potent inhibitor than clotrimazole in the main logarithmic phase, it was more fungicidal. The antifungal activity of miconazole on C. albicans was inversely proportional to the number of cells inoculated in the media. The effects of miconazole on growth depended on the nutrients in the medium and were most pronouncedwhen it was added to cultures of C. albicans in the lag and main logarithmic phase of growth. The growth inhibitory effects of sub-fungicidal doses of micronazole (smaller than or equal to 10-6 M) on C. albicans seemed to be reversible.


A re-evaluation of the effect of cysteine or Candida albicans. The effect of cysteine on Candida albicans has been re-examined. Concentrations between 0-1 and 10-0 mM were tested on 12 isolates in yeast and hyphal form. The growth of both forms was inhibited by 10 mM cysteine. Though the rate of hyphal elongation was decreased there was no suppression of initiation of hyphal formation. All isolates showed a random variation in their general inhibitory response to cysteine. We found no support for the concept of cysteine-mediated from determination in rapidly growing C. albicans in submerged culture. High concentrations of cystiene cause a general inhibition of growth of C. albicans.


Treatment of accelerated hypertension and end stage renal failure by bilateral nephrectomy and renal transplantation. Accelerated hypertension with end stage renal failure not responsive to hemodialysis and ultrafiltration was an indication for bilateral nephrectomy in 22 patients, five of whom required the procedure as an emergency. Normotension occurred in every patient after removal of the kidneys, but hypertension returned in 12 persons after renal transplantation. Five of these required long term antihypertensive medication, and in an additional seven, some form of diuretic was necessary. There were no distinguishing features among those patients in whom post-transplant hypertension developed from those in whom it did not. In spite of severe accelerated hypertension in the patient with well documented chronic renal disease, prompt nephrectomy and renal transplantation were compatible, with an 86 per cent patient survival rate. Seventy-seven per cent of the kidneys functioned for an average of 29 months.


Use of the axillary artery in complex cerebral revascularization. Two cases of complex common carotid and innominate artery disease managed by axillocarotid autogenous saphenous vein bypass are presented, including a detailed description of the operative technique. The results in each case were gratifying. Although the concept of extra-anatomic repair is not new, this modification in operative technique expands the surgeon's armamentarium. The ease and safety of exposure and anastomosis of the axillary artery combine to make it the preferable donor vessel for extra-anatomic cerebral revascularization in the poor-risk, elderly patient population.


The surgical amphitheatre, history of its origins, functions, and fate. The Surgical Amphitheatre, patterned after the earlier model of Anatomists, came into being in the 17th century and served the purpose of teaching the anatomy of operation to surgeons, but without hospital connections. A great decline of student and visitor interest in viewing operations attended disappearance of the gambler's risk of operations, followed at the turn of this century by a lesser interest of medical students in attending surgical lectures, a circumstance that provoked consternation in the ranks of surgical teachers. The demise of the surgical amphitheatre as a suitable site for surgical teaching and viewing operations marked the beginnings of a gradual decline of influence of surgery in medical school faculties. Acceptance by reluctant surgeons of the inescapable microbiologic principle that silence of the entire Operating Team is mandatory, when operations are in process, will obviously erode further usefulness of the operating arena for instruction of medical students. Over the past decade, the current sharpened focus upon dispersion of medical care has served to de-emphasize in our medical faculties the post-World War II stress upon research for medicine's advance. A gradual decrease of student interest in surgery has occasioned medical faculties to question the justification of continuing surgery as a major curricular discipline for undergraduate medical students. Surgeons need to cultivate the intimate teacher-student relationship reflected in the practices of Pierre Louis and William Osler. A critical reassessment by professors of surgery of their teaching responsibilities should serve to indicate to medical students and their faculties that surgery has much important and useful information to impart, and that their professors are ready, prepared, and anxious to meet the challenge.


Experience with lymphoceles after renal transplantation. Of 215 patients who underwent renal transplantations at the Mayo Clinic, six (2.8 percent) developed perirenal lymphoceles. Diagnosis was made between 5 weeks and 14 months after operation. In all six patients, renal function decreased and eventually a lower quadrant abdominal mass developed. Ipsilateral leg edema, fluid retention, and development of diastolic hypertension should also increase suspicion as to the possibility of lymph collection in the perirenal space. Excretory urography with tomography delineated the lymphocele in each instance; B scan ultrasound may be an additional valuable diagnostic tool. Drainage procedures readily restored normal renal function and, in one instance, drainage also restored the blood pressure to normal. Percutaneous needle aspiration seems to be a temporary measure only, and marsupialization is the preferred definite procedure.


Analysis of the optimal perfusion pressure and flow rate of the renal vascular resistance and oxygen consumption in the hypothermic perfused kidney. Thirty-six dog kidneys were perfused with different perfusion pressures (between 15 and 60 mm. Hg) for 72 hours and then transplanted. Hypothermic human albumin was the perfusion fluid.  Enzyme release, kidney weight, and renal oxygen consumption were measured during perfusion. Kidneys perfused with a flow rate of 0.8 ml. per gram per minute (21 mm. Hg mean perfusion pressure) showed the smallest increase in kidney weight and the best function after transplantation. Renal vascular resistance was independent of the level of the perfusion pressure and renal oxygen consumption was independent of the applied flow rate. It is concluded that the perfusion pressure applied with hypothermic perfusion should be as low as possible because in this way kidney damage caused by perfusion can be avoided most easily.


An improved nonsuture method for portacaval anastomosis in the rat. A nonsuture technique is described for performing portacaval anastomoses in rats. Improvements include reduced clamping time on critical vessels, reduced blood loss, uniformly patent anastomoses, easily manufactured buttons, and decreased mortality rates. The new procedure allows a single operator to perform 25 such operations per day, thus substantially increasing the availability of these animals for studies in hepatic metabolism following portacaval anastomoses.


Experience with a modification of Duhamel-Grob-Martin operation for the treatment of Hirschsprung's disease. Forty-two patients have been operated upon with the Duhamel-Grob-Martin operation to which has been added a partial sphincterotomy. Three patients developed anastomotic leaks and one of these died. In follow-up studies from 2 months to 9 years after operation, all patients were relieved of distension and constipation, except two, who were considered to have had an incomplete proximal resection of aganglionic bowel. There were two children with repeated attacks of enterocolitis after operation. Fecal control was good in all and, in spite of the retention of a considerable spur, there have been no problems from this. It is considered that the internal sphincter is involved in the disease and the possibility of persistent obstructive symptoms is reduced by the internal sphincterotomy which has not resulted in incontinence.


Adjustable razor dermatome: another efficient, economical, and portable dermatome. The adjustable razor dermatome is another simple, portable, inexpensive, yet efficient mechanical tool for skin grafting. The dermatome is constructed easily from an ordinary household adjustable safety razor. This model, unlike those described earlier will cut grafts of various thicknesses without the use of a different cutting head or shim.


The metabolism of saccharin in animals.

The metabolism of saccharin in animals. Rats given oral doses of [3-14C] saccharin excreted 56-87% of the labeled dose in the urine and 10-40% in the feces during 7 days. Distribution studies showed that the highest levels of 14C were in the kidneys and bladders. The bile was not a significant route of excretion. The presence of labeled CO2 in expired air indicated that saccharin was decarbosylated to a slight degree. DEAE chromatographic separation and isolation of labeled compounds from urine samples showed that more than 99% of the urinary 14C was unchanged saccharin. Up to 1.0% of the 14C was a metabolite identified as 0-sulfamoylbenzoic acid. Comparative metabolic profiles of a dog, rabbit, guinea pig and hamster indicated that there was little difference in the pattern due to animal species or dose level.


A comparison of betahistine hydrochloride with placebo for vertebral-basilar insufficiency: a double-blind study. To test the effectiveness of betahistine HC1 in reducing the frequency of transient ischemic attacks (TIAs) caused by vertebral-basilar artery insufficiency, we randomly assigned 26 patients with a typical history of the condition to a placebo-drug or a drug-placebo sequence, each sequence lasting two months. During the study, the frequency of TIAs did not differ significantly between the placebo and the drug groups. Subjective responses indicated some value for betahistine as a palliative agent.


Erythrocyte polyagglutination showing properties of both T and Tk, probably induced by Bacteroides fragilis infection. A new type of polyagglutination is described in which the T and Tk receptors are both exposed on the erythrocyte membrane. It is suggested that there may be an association between this type of polyagglutination and infection by Bacteroides fragilis.


Qualitative and quantitative study of the antigens and antibodies of the HL-A system-automatic fluorochrome method. It was possible to obtain a successful evaluation of the quantity of HL-A antigens on lymphocytes using a fluorochromatic test with double marking by fluorescine diacetate and ethidium bromide. It was also possible to detect anti-HL-A antibodies, to study their cross-reactions and to perform tissue typing using this automatic, sensitive and repeatable method.


[Method for preparing monospecific antiserum to fowl plague virus hemagglutinins]. A simple method for preparation of monospecific antiserum for the hemagglutinin of fowl plague virus has been developed. It is based on selective inactivation of the enzymatic and antigenic properties of neuraminidase by heating of the virus at 56degrees for 3 hours followed by disruption of the preparation with detergent and removal of the inner proteins by ultracentrifugation. Immunization of animals with such preparations produced antiserum containing considerable amounts of antibody for the hemagglutinin in the absence of antibody for other proteins of fowl plague virus.


[Fibrin removal from mouse immune ascitic fluids to arbovirus using beta-propiolactone]. A modification of acid precipitation of fibrin in immune ascitic fluids (IAF) employing beta-propiolactone has been developed. The procedure removes fibrin completely without affecting the titres of specific antibody. This modification is not inferior to previously described methods for fibrin removal from IAF and has a number of advantages. In addition to removing fibrin from IAF, beta-propiolactone prevents possible virus contamination of IAF and sterilizes the preparation additionally.


[Clinical and epidemiological aspects of influenza chemoprophylaxis with bonaphthone]. The results of double blind clinical, phisiological, biochemical immunological and virological studies carried out in 460 normal volunteers gave sufficiently objective evaluation of safety and antiinfluenza activity of bonaphthone. The new antiviral drug is recommended for wide epidemiological trials. In epidemiological, coded and strictly controlled experiment during influenza A/England epidemic in 1973 involving 1393 persons the prophylactic effectiveness of bonaphthone was established (the index of effectiveness 2.09).


[Biological and physicochemical properties of virus PBV-1, isolated from Penicillium brevi compactum]. High infectivity of PBV-1 virus for different strains of E. coli has been demonstrated. Sizes of the virus particle are; head diameter 513 angstrom, length of the process 1500 angstrom, diameter of the process 60 angstrom. The buoyant density of the virus in cesium chloride density gradient is 1.49 g/cm3, in cesium sulphate-1.39 g/cm3, the sedimentation constant of the virus particle is 380S; molecular weight is 52.8 plus or minus 1.9 times 10-6 daltons. The PBV-1 virus contains double-stranded DNA with the melting temperature in 1 SSC (0.15 M NaCl plus 0.0015 M sodium citrate, pH 7.0) and in 0.1 SSC-88.5 degrees C, respectively. The buoyant density of DNA in cesium chloride gradient is 1.7058 g/cm3 and in cesium sulphate 1.424 g/cm3. The content of GC-pairs calculated by the melting temperature is 46.5% and by the buoyant density 46.7%. On the basis of DNA sedimentation constant value (30S) the average molecular weight of DNA has been calculated to be 23.7 times 10-6 daltons.


[Hemagglutination tests with insect viruses]. Nucleopolyhedrosis viruses isolated from larvae of Mamestra brassicae L. and larvae of Ocneria dispar L. as well as granulosis virus isolated from Apamea anceps Shiff. were found to agglutinate red blood cells from a variety of animal species. Chicken and goose erythrocytes proved to be most sensitive. The haemagglutination-inhibition test with the virus of Mamestra brassicae and with specific mouse immune ascitic fluid (IAF) was positive. The titer of IAF was 1:160.


[Sensitivity of different strains of E. coli and Shigella to the inhibitory action of Ploskirev's bactoagar]. A study was made of the sensitivity of 190 strains of E. coli and 107 strains of Shigellae of different serological types to the inhibitory action of Ploskirev's bactoagar on the capacity of these bacteria to form colonies. The strains under study proved to be nonhomogenous in this respect: between different strains of E. coli there were revealed 10-, 100- and even 1000-fold differences by this property; the differences between Shigellae strains were less marked--in over 90% of Shigellae strains the capacity to form colonies was depressed less than 4-fold. Only with the aid of some of E. coli and Shigellae strains was it possible to detect differences between the tested 20 commercial Ploskirev's bactoagar batches. Apparently, the use in practical bacteriological laboratories of accidental strains of local origin for control of Ploskirev's bactoagar could not aid in improving the quality of the medium, and consequently bacteriological diagnosis of infections.


[Lytic antibodies in antibacterial sera. IV. Lytic activity of H-antibodies]. The authors studied the lytic and agglutinating activity of H-antibodies against S. typhimurium. Sera containing H-antibodies proved to possess a distinct lytic activity expressed in the presence of a complement and caused by specific antibodies. In H-antibodies specific lytic activity (as per 1 agglutinating unit) was much weaker than in O-antibodies. A relatively low lytic action of H-antibodies was apparently associated with topography of corresponding antigenic determinants of the microbial cell which determined the low possibility of fatal injuries. In examination of H-bacteriolysins there was revealed the same regularity as noted in studying the O-bacteriolysins: reduction of the lytic activity of antibodies in hyperimmunization.


[Regression analysis of the relation between antitoxic activity of sera (Jensen method) and antibody titers in the passive hemagglutination reaction]. Antidiphtherial and antitetanus antitoxic immunity was determined in the sera of 1588 children (20 experiments) and 611 children and adults (12 experiments) by two methods--on animals and in the passive hemagglutination test (PHT). Factual data were grouped in accordance with a conditioned scale of the antitoxin values in IU composed of the values average for each interval. The series of two-fold dilutions represented a scale of titres of the same sera in the PHT. Mathematical analysis showed that there was a direct linear regressive relationship between the indices of antitoxic immunity obtained by different methods. As a rule, regression coefficients were below a unit, i. e. the rate of increase of the values by the HDT titre scale was somewhat retarded from the growth by the IU titre, this pointing to the difference in their value. The free member of the regression equation (a) characterizing this choice of the sera varied widely. Between the regression coefficients calculated for individual experiments statistically significant differences were revealed in almost 50% of cases. Transformation of quantitative indices of one test into quantitative characteristics obtained by the other method, with the aid of regression equation calculated outside the definite experiment, proved to be unfounded.


[Genetic control of the ability of Sh. flexneri to produce a lethal effect on macrophages. I. Study of the possible extrachromosomal nature of the cyt+-determinant]. It was shown that cyt+-determinant could not be eliminated when the Sh. flexneri cultures were treated with ethidium bromide under the regimen providing the elimination of the F'lac-factor in a part of shigellae population. The cytotoxic Sh. flexneri strains which acquired the R-factor transmitted the multiple drug resistance to the cyt minus -strain of Sh. flexneri, but not the cyt+-properties. There was found no correlation between the cytoxicity of the Sh. flexneri strains and their capacity to mobilize the nontransmissive STr-ex-episome in the triple cross experiments. The results obtained were in favour of the chromosomal nature of cyt+-determinants controlling the capacity of Sh. flexneri to produce the lethal action on the macrophages.


[Typing properties of bacteriophages isolated from Sh. sonnei strains]. On the basis of studying the lytic activity of eight bacteriophages the authors elaborated a scheme of bacteriophage typing of Sh. sonnei consisting of nine bacteriophage types with two subtypes. In typing 2348 strains isolated in various cities of the USSR bacteriophage pattern of Sh. sonnei was found to differ in different towns of the USSR. All the strains isolated repeatedly from the same patients were referred to the same bacteriophage type, this pointing to the stability  of the type-determining properties of bacteriophages. Stability of bacteriophage types, a possibility of typing the strains of the I, II phases and of R-forms, simplicity and distinctness of the scheme of bacteriophage typing determined future prospects in using the type bacteriophages selected at the Tbilisi Institute of Vaccine and Sera for intraspecies differentiation of Sh. sonnei.


[Polyamines in species of microorganisms of the intestinal group]. A study was made of polyamines (putrescine, spermidine and spermin) in various representatives of the Enterobacteriaceae family--E. coli, Sh, sonnei, Sh. flexneri and S. typhi abdominalis. All the strains under study contained putrescine and spermidine, and many Shigella and Salmonella strains had spermin in addition. There were significant differences in the quantitative content of polyamines in the individual species. By the ratio of nitrogen of polyamine to phosphorus of nucleic acid it is possible to assess the correlation in the content of polyamines and nucleic acids in the bacterial cells.


[Antibodies to erythrogenic toxin B in scarlatina patients]. Coupled sera of 240 children suffering from scarlet fever obtained on the 1st-5th and 12th-15th days of the disease were examined in the PHA test with the A and B toxins. Antibodies to toxin B were revealed in 63-69% and to toxin A in 60-66% of the sera. In 64.5% of the cases the sera under study reacted simultaneously with both types of the toxin; antibodies to toxin B were contained in higher titres than to toxin A in 1/3 of the sera. The highest antibody titres to toxin B were revealed during summer.


[An experimental study of auto-allergy evoked by staphylococcus under conditions of primary and secondary immunological response]. Experiments were conducted on rabbits and albino mice; it was shown that the capacity of the animal organism to reject the skin autotransplant formed 7 to 10 days after the primary immunization and persisted for a period of 45 days. Repeated vaccination of mice 24 hours before the operation aided the take of the skin autotransplants, and 7 days before--promoted their rejection. Intravenous revaccination of the operated animals also intensified the rejection reactions; the process of the transplant rejection was accompanied by a marked fall in the level of staphylococcus- and autoantibodies. In the unoperated animals intravenous revaccination with staphylovaccine caused production of antibodies by the secondary type. Deposits of fixed gamma-globulin were found on the 6th-8th day after the transplantation in the autotransplant and its bed in mice primarily immunized with staphylovaccine. Marked circulatory disturbances, necrobiotic processes, mononuclear infiltration of the derma with neutrophils were revealed pathomorphologically in the rejecting skin transplant.


[Palatine tonsils and immunity. III. T- and B-lymphocytes in the palatine tonsils of patients with chronic tonsillitis]. Both B- and T-cells are contained in the palatine tonsils of patients suffering from chronic tonsillitis. The former respond by blast-transformation to the in vitro stimulation by the streptococcus and staphylococcus antigens and the latter--to PHA, and produce soluble substances inducing blast-transformation reaction of lymphoid cells of the palatine tonsils under the effect of streptococcus and staphylococcus antigens.


[The ultrastructure of L-forms. III. The L-forms of S. typhi and Pr. vulgaris]. A marked polymorphism was revealed in the colonies of 5--7 day L-forms of S. typhi and Pr. vulgaris: among different types of the cells there prevailed spherical or oval forms with a distinct nucleoid. Three-layer cytoplasmic membranes--the site of formazan TNBT deposition in the reaction for succinic dehydrogenase--were detected on the greater part of the cell surface. Sometimes there were revealed on the surface of the membrane residues of the cell wall in the form of structureless material of low electron density or pieces of external membrane. Myelin-like structures, mesosomes of ring or lamellar structure and two-contour vesicles located directly in the cytoplasm were found in the cytoplasm. L-form cells displayed binary fission or reproduced by budding; in the latter case there formed elementary bodies surrounded by a three-layer membrane, not infrequently with a visible nucleoid and structures resembling mesosomes of the lamellar type.


[A comparative immunochemical study of the subtypes of serologic type I of the agent of pseudotuberculosis]. It was shown that Y. pseudotuberculosis strains causing the Far-Eastern scarlatina-like fever in the Primorsk region belonged to subtype IB-ipopolysaccharides of the standard strain of subtype IB and of the local strain were closely affiliated by the analytic data and monosaccharide composition, but differed from the lipopolysaccharide of strains belonging to subtype IA. Living vaccines should be used to obtain the sera against the subtypes IA and IB of the causative agent.


[The role of the ability of Sh. flexneri to synthesize pili of the common type in the development of dysenteric infections]. HEp-2 epithelial cells infected with isogenic Sh. flexneri strains characterized by capacity to synthesize common pili (confirmed by electron microscopy) were studied. It was shown that although pili promoted an earlier adhesion of shigellae to the cells, they were not very significant for the penetration and intracellular development of dysentery bacilli in the epithelium. The use of bacteria labeled with 3H-glucose offers a possibility of an objective rapid and precise determination of the capacity of the microbes to adhere to the cell surface.


[A method of determining the efficiency of the projected process of uninterrupted microorganism cultivation for vaccine production]. The authors suggest the method of study of the process of periodic cultivation of microorganisms for prognostication of the optimal process of biomass accumulation at the level of microbial population, homogenous by the spectrum of biochemical properties. A regimen of continuous growth of the microorganisms (calculated with the use of this method), corresponding to the phase of delay of the growth rate, was economically more effective in comparison with the traditional process used in the vaccine production.


[Antibodies to type antigens of group A streptococcal cell walls in erysipelas patients]. The passive hemagglutination test was used to determine antibodies to type antigens of the cell wall of streptococcus group A in 167 patients suffering from erysipelas, from whom 488 sera were obtained. Antibodies were revealed in 97.2% of the sera. There was a definite relationship between the clinical form of the disease and the level of antibodies: their lowest level and the absence of elevation in the course of the disease was noted in continuous-relapsing form of erysipelas; the appearance of antibodies to the new types of streptococcus was usually noted in late relapses of the disease, which permitted to attribute their occurrence to infection by the new types of the microbes. In individual cases the appearance of antibodies to the new types of streptococcus was observed at the early relapses of erysipelas; this could be explained by the exacerbation of a focus of chronic (endogenous) infection in the skin in the absence of reinfection. Continuous prophylactic administration of bicillin-5 produced no depressive effect on the antibody level in patients with relapsing erysipelas.


The effect of platelet function inhibitors on experimental venous thrombosis formation in rabbits. Inhibitors of the platelet functions, collagen-induced aggregation and release reaction (ASA and sulfinpyrazone) and ADP-induced aggregation (dipyridamole and VK 744), were investigated as potential preventive agents against venous thrombosis formation in rabbits. An experimental model combining endothelial damage (sodium morrhuate) and controlled stasis of the femoral venous flow was used. None of the agents showed any significant protective effect against venous thrombosis, a finding which is in keeping with the results of recent clinical investigation.


Plasma substitute induced impairment of the reticuloendothelial system function. Currently used plasma substitutes are large colloids and are partly engulfed by reticuloendothelial (RE) cells. This study was designed to investigate the magnitude and duration of the possible RES dysfunction induced by plasma substitutes. The following substances were studied in both normal and burned (LD-10) CBA mice: allogen albumin 3%, and commercial preparations of dextran 40, dextran 70, hydroxyethyl starch, gelatin and PVP. Infusion volume was 20 ml/kg and i.v. infusion time 1 hour. Animals given allogen plasma served as controls. One, 3 and 6 hours after the i.v. injection of 51-Cr-rabbit RBC, we determined the disappearance rate, and uptake and distribution of the 51-Cr-RBC in the main RES organs (liver, spleen and lungs). In normal mice the disappearance rate was significantly decreased one and three hours post infusion, while it was decreased even after 6 hours in burned mice. Groups given albumin or plasma stayed close to non-infused animals. In order to clarify the physiologic significance of these findings we used another test substance known to be handled by the RES. Salmonella enteritidis endotoxin was tested with regard both to toxicity and rate of elimination. The toxicity, after i.p. injection, was significantly intensified both one and 3 hours post-infusion in normal mice. In burned mice toxicity became even more intense. The ability to eliminate 51-Cr-labelled endotoxin was significantly decreased following infusion in both normal and burned mice, one as well as three hours later. The in vitro liver phagocytosis was tested utilizing the liver slice technique. Standardized slices were incubated in Krebs-Ringer buffer together with 125-I-HSA aggregates as RES test substance with and without plasma from mice given plasma substitute infusions. Allogen plasma enhanced the phagocytic uptake (four times), while post-infusion plasma did not. It is concluded from these experiments, utilizing two different RES test substances in both normal and hypovolemic animals, that the plasma expanders tested do impair RES phagocytosis. The mechanism seems to be an interaction with phagocytosis-promoting plasma factors. Even though this impairment is temporary, it may jeopardize such important RES functions as elimination of microorganisms, toxins, cell debris and tumour cells, or spoil the afferent limb of the immune response to many antigens.


Immunoglobulin synthesis and its induction in B-lymphoid cells. Several aspects of synthesis and assembly of Ig molecules in small lymphocytes and in differentiated plasma cells are summarized. Some attempt has been made to analyse at the molecular level what happens on conversion of a lymphocyte to a mature cell secreting high levels of Ig. For this study LPS activation of murine B-lymphocytes into division and maturation served as a model system. A rapid rate of mitosis and high rate of H-mRNA synthesis appeared to precede the high levels of Ig production, suggesting a translational block on H-mRNA until the cell had organized its endoplasmic reticulum and matured. In vivo, with the exception of T-independent antigens, it is unlikely that B-cell maturationis an automatic sequel to division stimuli. We are largely ignorant in this area but possible regulatory signals which achieve a dissociation of B-cell division and maturation are discussed.


Effects of immunization with LDH-X on fertility. Immunological regulation of fertility can be best achieved if a defined macromolecule is used to provide the antigenic stimulus. Proteins with known enzymatic properties are attractive molecules in this area if it can be demonstrated unequivocally that they are unique constituents of spermatozoa, and are completely foreign to the female. This paper describes immunosuppression of fertility by the sperm-specific isozyme of lactate dehydrogenase (LDH-X). In addition, evidence is reviewed which suggests that acrosomal proteinase and hyaluronidase may be unique to sperm. Data are presented which confirm the sperm specificity of LDH-X and the immunochemical homogeneity of purified preparations of this isozyme. Immunization of female rabbits with LDH-X significantly reduces the fertility of these animals. Experimental results indicate that the primary effect of immunization involves blockage of fertilization. While those ova which are fertilized in an immune environment develop and implant normally, there is a high rate of post-implantation embryo mortality. Rabbit blastocysts transferred to immune recipients implant at the same rate as in non-immune controls. These findings are consistent with the conclusion that the developing embryo must interact with antibody during the pre-implantation stages of pregnancy when antigenic sites conferred by the sperm LDH-X are available. Such interaction can be demonstrated directly by immunofluorescence techniques.


Macrophage activation induced by lymphocyte mediators. This paper is a brief review of studies which demonstrate that lymphocyte mediators can activate macrophages in vitro. Macrophages which have been incubated in lymphocyte mediator-rich Sephadex fractions show changed morphology, metabolism and function. These changes include an increase in adherence to glass. ruffled membrane movement, phagocytosis of some particles, glucose oxidation through the hexose monophosphate shunt and an increase in the activity of a membrane enzyme, adenylate cyclase. Such mediator-activated macrophages show enhanced bacteriostasis and tumoricidal activity. In addition, studies describing the role of membrane sugars and esterases in the interaction of migration inhibition factor and macrophages are reviewed.


Local immunological response in the vagina, cervix and endometrium. The mechanism of the local excretion of secretory IgA (SIgA) in exocrine secretions has been reviewed. Numerous local IgA-plasma cells, in the lamina propria of the glandular mucosa, synthesize dimeric IgA with J-chain. Free secretory component (FSC) is synthesized and accumulated in the Golgi area of the columnar epithelial cells. It is then supposed to get onto their cell membranes. Dimeric IgA (and some IgM) reaches tn dimeric IgA (and some IgM) and the FSC located in the cell-membrane, whereby SIgA is formed. The complex becomes mobilized and is transported toward the apical part of the cell, where it will be excreted into the mucous coat covering the epithelium. In the female genital tract, the cervical mucosa appears to be better adapted to achieve a local secretory immune system. The endometrium seems less suitable, being normally short of local plasma cells. The vaginal wall appears almost incompatible with the proposed mechanism of local antibody secretion. Criteria for establishing a local immune response in the female genital tract comprise: 1) a lack of correlation between antibody titers in secretions and serum; 2) the demonstration that the secretory antibodies are mainly of IgA class and 3) that they are SIgA molecules, possessing bound secretory component. However, the best criterion would be 4) the observation that antibody is actually synthesized in samples of mucosa, by in vitro culture or immunohistology. Reviewing the literature, relatively few examples were found where SIgA antibodies were demonstrated, and unambiguous evidence for their local synthesis is almost non-existent. In addition, the authors were unable to detect antibody-containing cells in cervical and endometrial biopsies of women locally "immunized" with horse spleen ferritin and bovine serum albumin. The need for further investigation with simple antigens and adequate immunological reagents is stressed.


Fertility control through active immunization using placenta proteins. Numerous studies have demonstrated that antibodies to placental proteins in a variety of species are capable of preventing or disrupting gestation. Early work in this area was primarily directed towards the passive immunization of rodents with heterologous antisera to whole placental extracts. Toxicity and renal damage often accompanied fertility inhibition. More recent studies reported less toxicity and a higher specificity of antibodies to reproductive function when anti-placental antibodies were absorbed with serum and extracts of non-reproductive organs. Few studies have been reported in which active immunization with placental proteins was employed. The most detailed studies of active immunization have employed highly purified placental hormones. Immunizations of rats and rabbits with human placental lactogen have resulted in marked reduction in reproductive function. Immunization of human females with chemically altered (hapten-coupled/ HCG resulted in the production of antibodies reacting with unaltered HCG and pituitary LH. These antibodies were capable of reducing the level of endogenous serum LH in pre- and post-menopausal women. The also altered the events of the menstrual cycle in premenopausal women. More specific inhibition of chorionic gonadotrophin has been obtained by immunization of baboons with the beta subunit of HCG. Antifertility effects without alterations in the menstrual cycle of female baboons immunized with the beta subunit of HCG have been reported. The antibodies produced in these animals reacted significantly with human LH in vitro. The possibility of using hormonal and non-hormonal placental proteins as antigens for the specific immunological inhibition of fertility remains.


The use of antibodies developed by infertile women to identify relevant antigens. In the first half of this century several studies demonstrated that temporary infertility may be induced by immunizing women with semen. Isolated examples of acute hypersensitivity reactions to sexual intercourse provide dramatic evidence that natural isoimmunization to semen occurs in man. The afferent immunological pathway in this process can be influenced by adjuvant effects of genital tract infection. This may be important in assessing the significance of antisperm antibodies in infertile women. In immunological studies of female infertility, the 3 most commonly used tests for humoral antisperm activity are microagglutination, macroagglutination and immobilization (complement dependent cytotoxicity). The sperm microagglutination test detects both antibody and non-antibody activity. The macroagglutination and immobilization tests both detect antibodies but to date the latter has provided the more meaningful results in infertile women. A prospective study of reproductive patterns in infertility patients indicated a lower subsequent fertility rate and a markedly higher abortion rate in women with antisperm antibodies compared to those without them. However, the association of antisperm antibodies with continuing infertility only reached a statistically significant level in women with a past history of unexplained infertility of at least 3 years' duration. Occlusion (condom) therapy in patients with antisperm antibodies has proved unsuccessful when compared with the natural reproductive patterns in untreated patients. Immunofluorescence studies are described and correlated with results of other tests for antisperm antibodies in serum and cerivcal mucus. The results of these and of other studies of naturally occurring antibodies in infertile women have identified antigens of actual or potential relevance to infertility and fertility control. These include (i) intrinsic spermatozoal antigens, (ii) seminal plasma antigens, (iii) blood group antigens, (iv) histocompatibility antigens and (v) nucleoprotein antigens.


Kinetics of antibody formation and regulatory aspects of immunity. This paper, which is to be read in conjunction with that of Dr. J.F.A.P. Miller earlier in this volume, addresses itself to the kinetics of antibody production and to the regulation of the immune response. It is divided into four main sections. The first examines the kinetics of antibody production to a single, strong challenge injection of antigen. The cellular events involved in the latent period and the subsequent exponential phase of antibody production are examined from the viewpoint of four key concepts: triggering, clonal expansion, IgM to IgG switch and affinity maturation. The second section examines the major regulatory influences and feedback loops in immunity. Antigen is discussed as an agent capable of causing tolerance as well as triggering. Antibody is considered an important regulator, and the mechanisms of IgM-positive feedback, IgG-negative feedback, and tolerance and blockade effects of immune complexes are outlined. Immunological memory, the opposite phenomenon to tolerance, is briefly described, as is the importance of genetic factors. The third sections looks at more complex models of the immune response, and in particular at the lessons to be learnt from tumour progression.


Production of lymphoid tissue in the rat brain by implants containing phytohemagglutinin. Large numbers of plasmacytes and lymphocytic cells develop at the tip of miniature pipettes containing phytohemagglutinin (PHA) implanted into the brain of adult Lewis rats. The accumulation of lymphoid elements is present in tissue exposed to PHA for 1 week, and it persists in animals which were allowed to survive up to 10 weeks. It did not occur around control or non-active implants. Lymphoid cells usually serve as a morphologic index of immune mediated phenomena, but no evidence was seen in the present study to indicate that they produce damage to axons, dendrites or glial cells of the central nervous system despite direct contact with them. Plasma cells in the brain appear to develop from "dark" cells resembling lymphocytes that migrate into the central nervous system from reactive lymphoid tissue near the tip o.f the implant. Nerve, glial and subependymal cells do not respond with mitogenic activity to PHA.


Persistent neonatal hypoglycaemia. A clinical and histopathological study of three cases treated with diazoxide and subtotal pancreatectomy. Two boys and one girl developed persisting hypoglycaemia 12, 24, and 48 hours after birth. Although there was no known history of hereditary diabetes mellitus, the birth weight was high in two cases, and some additional traits of foetopathia diabetica could not be excluded clinically. All had high serum insulin levels with frank hyperinsulinaemia in one case. Glucose tolerance tests also indicated hyperinsulinism. Diazoxide (8 to 27 mg/kg) elevated the blood glucose levels, but did not prevent severe hypoglycaemic episodes. The effects of subtotal pancreatectomy were only transient. The patients have now been kept on permanent diazoxide therapy for 2-4 years at dosages slightly lower than those used before operation. No islet-cell tumour was found at the subtotal pancreatectomy. In all 3 cases, the pancreatic islets were markedly hyperplastic and of irregular shape with the occurrence of large B-cells with giant hyperchromatic nuclei and chromophobe "agranular" or sparsely granulated cells. The predominating kind of islet cells showed tinctorial features of A2-cells but--in the absence of available material set aside for ultrastructural analysis--it could not be settled whether this was a result of a proliferation of A2-cells only or of "type IV cells" as well. Against the background of previously published reports, the present cases serve to illustrate that additional accuracy of diagnosis and classification of neonatal persistent hypoglycaemia requires quantitative information about the structural changes in the pancreatic islet cells, and that this can be obtained from conventional biopsy specimens.


Experimental murine leprosy. 3. Early local reaction to mycobacterium lepraemurium in C3H and C57/BL mice. M. lepraemurium was injected subcutaneously into two inbred strains of mice, C3H and C57/BL, in order to study the local reaction at various time intervals. Within 6 hours an acute inflammatory reaction developed at the site of injection. In the course of the following days it was replaced by a mononuclear infiltrate. The influx of mononuclear cells appeared to be somewhat greater in C57/BL than in C3H mice. Apart from this, little difference was observed between the two strains until at 4 weeks when a vigorous granulomatous reaction developed in the C57/BL strain. This reaction apparently arrested further local spread of the infection. The histological appearance of the inflitrate indicated that a delayed hypersensitivity reaction was taking place. No signs of such reaction was observed in the C3H strain.


Experimental murine leprosy. 4. The gross appearance and microscopic features of the local infiltrate after subcutaneous inoculation of C3H and C57/BL mice with mycobacterium lepraemurium. Mice with the inbred strains C57/BL and C3H were inoculated subcutaneously on the thorax with M. lepraemurium. In C57/BL mice a firm, raised, sharply defined nodular infiltrate developed 4 weeks afterwards, while in the C3H strain of the infection produced a soft, flattened infiltrate with ill-defined margins, which did not become palpable until 10 weeks after inoculation. A limited spread of the infection occurred early in both strains, but apparently multiplication of the microorganisms was very restricted in C57/BL mice; progressive, disseminated growth of the bacilli was observed in the C3H strain only. In C57/BL mice the granulomatous reaction, developing 4 weeks after inoculation and leading to abcess formation, ulceration and scar formation, apparently inhibited both local multiplication and further spread of the bacilli. In C3H mice no host reaction was detected and the bacilli appeared to grow unrestrictedly. In some C57/BL animals, decrease in host resistance occurred during the infection, causing reactivation of the local lesion and an apparently rapid proliferation of bacilli. Observations regarding the lesions in superinfected animals indicated that a systemic immune reaction develops in the C57/BL strain about 4 weeks after inoculation, whereas this does not occur in the C3H strain.


Liver impairment during chronic hemodialysis and after renal transplantation. Liver impairment has been evaluated in a consecutive series of 79 patients with chronic renal failure of whom 23 were treated with hemodialysis alone and 37 with hemodialysis and renal transplantation alone. In half of the chronic hemodialysis patients and half of the patients receiving a renal allograft elevation of serum alanine aminotransferases was observed for a shorter or longer period during the study. In half of these cases from both groups the clinical course, laboratory data and liver histology were consistent with virus hepatitis and four patients died from fulminant hepatic failure. In the other half of the patients with elevated transaminases, this was either asymptomatic and unexplained or due to other causes such as septicaemia or urinary leakage. Liver biopsy showed unspecific changes. Renal transplantation was not performed in patients suffering from virus hepatitis, but 12 of the 37 patients who received a renal allograft had elevated aminotransferases at the time of transplantation. In seven of them a marked increase in aminotransferase was observed postoperatively, but none developed clinical sign of liver disease. It is concluded that elevated aminotransferase activity per se is no contraindication to surgical procedures, including renal transplatation, in these patients. However, a liver biopsy should be performed to detect a possible liver disease.


Transfer of E1 and V colicinogenic factors to Shigella flexneri. From Escherichia coli strains, ColE1-ML and ColV-K94 factors were transferred to a virulent Shigella flexneri 2a strain at 1-2% frequency. S. flexneri ColV+ and ColE1+V+ produced Col- segregants. The ColE1 factor was stably incorporated into S. flexneri. The ColV+ culture lost its virulence to the guinea pig eye.


Effect of some aminoglycosides upon a drug dependent Escherichia coli strain. Escherichia coli Sd-4-73 drug dependent strain was sensitive to kanamycin, gentamicin and neomycin in the absence of drugs stimulating cell multiplication. This senstivity was not considerably influenced by streptomycin, while paromomycin afforded protection against both bacteriostatic and bactericidal effects. The paromomycin concentration optimum for protection was different from its concentration optimum for multiplication.


Changes in certain iron metabolism variables after a single blood donation. Signs of iron deficiency have been studied after the first blood donation in 11 healthy men. Six were given 100 mg iron daily, and five received placebo tablets. The total iron-binding capacity and iron absoprtion remained raised for more than 26 days, but had almost returned to the initial values after 70 days. A significant decrease in the stainable bone marrow iron could be shown in all subjects after 26 days; later some restitution was seen in subjects given iron supplements, but not in those given placebo. As the restitution times are long, the interval after blood donation must be taken into account when judging iron metabolism variables in active donors.


Iron supplement to blood donors. I. Trials with intermittent iron supply. A series of 58 male blood donors has been studied with regard to stainable bone marrow iron, desferrioxamine test, sideroblasts, total iron-binding capacity, serum iron, and haemoglobin values. With one conventional blood donation every second month the storage iron was found to be significantly decreased after four blood donations both when placebo and oral ferrous iron in doses of up to 2000 mg were given over a period of two weeks after each blood-letting. The iron state in donors given 2000 mg was superior to that in donors given 1000 mg, and better in the latter group than when placebo was given. A moderate increase in the total iron-binding capacity could be discerned in subjects treated with placebo or only 1000 mg iron after each donation, but no changes in serum iron or haemoglobin were noted. A smaller series of 13 donors was also investigated after six donations and was found to show essentially the same pattern in the iron state variables as after four donations. When the interval between donations was four months and 2000 mg ferrous iron was given over two weeks after each donation, all variables including the amount of bone marrow iron and the desferrioxamine test remained unchanged in ten subjects after four donations. Two subjects showed a moderate decrease in the stainable bone marrow iron, but it did not disappear completely.


Clinical application of a second generation electrocardiographic computer program. An electrocardiographic computer program based on multivariate analysis of orthogonal leads (Frank) was applied to records transmitted daily by telephone from the Veterans Administration Hospital, West Roxbury, Mass., to the Veterans Administration Hospital, Washington, D. C. A Bayesian classification procedure was used to compute probabilities for all diagnostic categories that might be encountered in a given record. Computer results were compared with interpretations of conventional 12 lead tracings. Of 1,663 records transmitted, 1,192 were selected for the study because the clinical diagnosis in these cases could be firmly established on the basis of independent, nonelectrocardiographic information. Twenty-one percent of the records were obtained from patients without evidence of cardiac disease and 79 percent from patients with various cardiovascular illnesses. Diagnostic electrocardiographic classifications were considered correct when in agreement with documented clinical diagnoses. Of the total sample of 1,192 recordings, 86 percent were classified correctly by computer as compared with 68 percent by conventional 12 lead electrocardiographic analysis. Improvement in diagnostic recognition by computer was most striking in patients with hypertensive cardiovascular disease or chronic obstructive lung disease. The multivariate classification scheme functioned most efficiently when a problem-oriented approach to diagnosis was simulated. This was accomplished by a simple method of adjusting prior probabilities according to the diagnostic problem under consideration.


Simultaneous autoradiographic and immunohistochemical localization of estrogen and gonadotropin in the rat pituitary. A combined autoradiographic and immunohistochemical technique is introduced which is suitable to simultaneously localize hypophyseal sites of nuclear (3-H)-estradiol uptake and anti-hCG-characterized "gonadotropes". Most, but not all, "gonadotropes" show significant nuclear concentration of radioactivity. A large percentage of non-"gonadotropes" also show nuclear uptake of label.


Effect of acupuncture of pain threshold and pain tolerance determined by electrical stimulation of the skin: a controlled study. The effect of needling traditional acupuncture loci (Ho-Ku, LI4; Nei-Kuan, EH-6) compared to arbitarily chosen points was measured in twelve healthy subjects.  In a crossover blind study pain tolerance and pain threshold were measured by electrical stimulation of  the skin in the thyroid area.  Traditional acupuncture was found to be significantly more effective in elevating pain  threshold than needling of arbitarily chosen points.  Pain tolerance also rose more under "real" acupuncture, the difference, however, being statistically not significant.  In one subject, threshold and tolerance increased more under needling of nonacupuncture loci, while two subjects did not show any changes under either procedure.


Susceptibilities of bacteria to different antibiotic regimens. Study in two nursery populations. Hospital nursery A has used chloramphenicol and nursery B has used the combination of penicillin G sodium and kanamycin sulfate routinely in the treatment of neonatal sepsis and other bacterial infections. A hypothesis was formulated that these different antibiotic pressures would select out a substantial number of populations of resistant bacteria in each of the two nurseries. This was tested by periodic sampling of the skin, mouth, and rectal flora of babies and the permanent personnel in these nurseries. These bacteria were studied for susceptibility to a number of antibiotics. The population of resistant strains selected out was correlated with the antibiotics used in each nursery. There is a need for continuing surveillance of hospital nursery strains of bacteria for in vitro susceptibilities to commonly prescribed antimicrobials.


Management of acute epiglottitis by nasotracheal intubation. In 40 cases of acute epiglottitis in children, intubation was the chosen method for the management of airway obstruction. Six patients were treated without the establishment of an artificial airway, and no tracheostomies were done. No patients who were admitted to the hospital died of airway obstruction, although one sustained irreversible brain damage before admission, and two died of overwhelming infectionmthe average duration of intubation was 2.days and the average hospital stay was 5.days. Two children developed subglottic granulation tissue that was removed successfully and did not recur. Nasotracheal intubation is an acceptable method of management of epiglottitis.


Outbreak of lymphocytic choriomeningitis virus infections in medical center personnel. An outbreak of lymphocytic choriomeningitis (LCM) virus infections occurred in Medical Center personnel at the University of Rochester in 1972-1973. A total of 48 infections was discovered, 31 in staff of the radiation therapy area, 12 in the staff of the Vivarium facility, and 5 in other individuals who worked in the Medical Center. Twenty-one of the infections were associated with recent febrile illness with myalgia. Epidemiologic and virologic studies indicated that the source of the infection was Syrian hamsters which were used in tumor research; the tumor cell lines themselves were shown to be contaminated with LCM virus and probably represented the original source of contamination of the Rochester facility. Infection occurred not only through direct contact with infected animals but also from mere presence in the room where the animals were held. This outbreak emphasizes the need for restricting access to animal quarters and for surveillance of hamsters and tumor cell lines and indicate the necessity of separating animal facilities from patient-care facilities.


Shigellosis at sea: an outbreak aboard a passenger cruise ship. Between June 23 and June 30, 1973, 90% of 650 passengers and at least 35% of 299 crew members experienced a diarrheal illness during a 7-day Caribbean cruise aboard a passenger cruise liner. Symptoms were consistent with shigellosis, and Shigella flexneri 6, Boyd 88 biotype, was isolated from rectal swabs taken from 8 to 35 ill passengers and 33 of 294 crew members. Epidemiologic evidence incriminated the ship's water, including ice, as the probable vehicle of transmission, and elevated coliform counts were found in potable water samples obtained aboard the vessel at the peak of the outbreak. Potential sources of contamination of the vessel's potable water supply were investigated, and improvements in the loading and chlorination of potable water were recommended.


An epidemiologic study of renal failure. I. The need for maintenance hemodialysis. A nationwide morbidity study of end-stage kidney disease in Israel revealed a mean annual incidence rate, in the two-year period 1965-1966, of 70 cases per million per year requiring maintenance hemodialysis in the age 15-59 Jewish population. Chronic glomerulonephritis (38%) chronic pyelonephritis (24.9%) and polycystic disease (8.1%) represented the three most common diagnostic entities. It is suggested that the load of new cases on available dialysis units will not increase indefinitely but that an equilibrium will be established between the intake of new candidates and the outflow due to deaths and transplantation.


Waterborne shigellosis at a public school. In November 1972 an outbreak of gastrointestinal illness occurred at a public school in Stockport, Iowa. One hundred ninety-four (72%) of 269 pupils and 14 (16%) of 23 staff members were affected. The etiologic agent was a strain of Shigella sonnei resistant to multiple antimicrobials. Waterborne transmission of shigellosis was documented epidemiologically and by isolation of the organism from the school water system. Ninety-seven (14%) of 698 of the students' household contacts developed diarrhea, and possible secondary cases also occurred in 3 (9%) of 32 household contacts of school staff.


Chemotherapy of infections in cancer patients: a review. The factors altering host-defense mechanisms and the nature and significance of the resultant infections in cancer patients by a wide variety of invasive organisms are described. The principle and method of selection of antimicrobial agents as therapy in initial empiric treatment of presumed infection in febrile cancer patients, as well as therapeutic agents fothe therapy of infections by specfic organisms, are discussed. Special emphasis is placed on the more recently developed agents for the therapy of infections by Pseudomonas and other gram-negative bacilli.


Digitalis pharmacokinetics and metabolism. The pharmacokinetics of the cardiac glycofides have been elucidated as a result of the development of assays of sufficient sensitivity to measure the concentration of digitalis compounds in biological fluids. Digoxin can accumulate in the body without the administration of a loading dose, and a steady state blood concentration will be reached in 5 to 7 days. Digitoxin requires 35 days to accumulate to a plateau. If a loading dose of digoxin is used, it should be approximately three times the estimated daily maintenance dose. Factors that determine the selection of the appropriate maintenance dose of digoxin include renal function and lean body mass. Digitoxin is less dependent on renal function for its elimination than is digoxin. Knowledge of the pharmacokinetics of digitalis preparations is useful in determining how to change from one cardiac glycoside to another, each with different half-lives. One should wait 3 days before starting digoxin therapy when changing from maintenance digitoxin to digoxin (assuming normal renal function). The pharmacokinetics of changing from ouabain to digoxin without loss of digitalis effect are described. The metabolism of the commonly used digitalis preparations are summarized.


Serum digitalis measurements in the assessment of digitalis resistance and sensitivity. Antibodies to digitalis glycosides have been elicited in experimental animals and have been utilized in the development of rapid, sensitive, specific and convenient radioimmunoassay methods for the clinical measurement of digoxin and other cardiac glycosides in man. The use of these assay methods has supplemented earlier studies with radiolabeled digitalis preparations and has made it possible to obtain much new information concerning factors which may contribute to the well known patient to patient variability in digitalis dosage requirements and in sensitivity to the toxic effects of cardiac glycosides. In some patients with a poor clinical response to digitalis, the finding of a serum concentration which is relatively low for the dose prescribed may suggest that true digitalis resistance is not present and may raise questions of poor patient compliance, tablet inadequacies, intestinal malabsorption, increased metabolic degradation or hyperthyroidism; if the cause of the low serum level cannot be identified or corrected, serial serum measurements should enable safe and rational upward adjustment of dosage. In some patients with digitalis toxicity, the finding of a serum level which is relativity high for the dose prescribed may suggest that the patient is not sensitive to digitalis but rather is excreting it slowly; in such instances in elderly patients (with decreased glomerular filtration rates) and in patients with renal disease, serial digitalis measurements are useful adjuncts to clinical observation in determining optimal digitalis dosage schedules. A knowledge of serum digitalis concentrations should enable us to develop sound principles for a more rational approach to the clinical administration of cardiac glycosides, especially in patients with unusually high dosage requirements or with unusual sensitivity to relatively small doses of digitalis.


Digitalis toxicity: epidemiology and clinical use of serum concentration measurements. Despite continuing advances in understanding of the basic pharmacology of the cardiac glycosides, digitalis intoxication remains a common clinical problem. Physician education programs and increasing use of serum or plasma concentration data have, however, been shown to be capable of substantially reducing the incidence of digitalis toxicity. Methodologic progress and availability of commercial radioimmunoassay kits have placed measurement of clinically relevant serum or plasma cardiac glycoside concentrations within the capability of most well equipped clinical laboratories. Extensive experience with serum digitalis levels now provides a basis for ongoing examination of the role of these measurements in clinical practice. Results of studies to date demonstrate that mean serum digoxin and digitoxin levels are significantly higher in patients with electrocardiographic evidence of toxicity compared with patients without such evidence. It must be emphasized, however, that because of overlap in serum digitalis levels between these two groups, sole dependence on these levels for established of a diagnosis of digitalis toxicity is not warranted. Multiple factors influence individual responses to cardiac glycosides, and serum concentration data must be interpreted in the over-all clinical context. Type and extent of underlying heart disease are important determinants of the clinical response to any given dose or concentration of cardiac glycoside. Knowledge of the serum digitalis concentration is likely to be helpful in the setting of suspected digitalis intoxication in the absence of an adequate history, or in the presence of fluctuating renal function, overt or suspected malabsorption, or uncertain bioavailability. More generally, such measurements may prove useful whenever an unanticipated response to digitalis is encountered, whether it be suspected toxicity or the absence of an expected therapeutic effect.


Pharmacologic and clinical control of antiarrhythmic drugs. Knowledge of pharmacokinetics and pharmacodynamics is a powerful tool for controlling cardiac arrhythmias with drugs even though antiarrhythmic drugs are potentially quite toxic. If the diagnosis and drug selection are correct at the outset of therapy, the clinician can use his knowledge of pharmacokinetics to achieve arrhythmia control with a minimum of personal effort and risk to his patient.


Effects of ascorbic acid on the common cold. An evaluation of the evidence. Of 14 clinical trials of ascorbic acid in the prevention and treatment of the common cold, the data from 8 were considered well enough gathered to be creditable and to warrant combining for an over-all assessment of efficacy. Differences in mean prorated numbers of colds per year and durations of illness were 0.09 plus or minus 0.06 (plus or minus 1 standard error) and 0.11 plus or minus 0.24, respectively, favoring ascorbic acid over the placebo. These are minor and insignificant differences, but in most studies the severity of symptoms was significantly worse in the patients who received the placebo. In one study lasting 9 months, a large number of the volunteers tasted their capsules and correctly guessed what group they were in. All differences in severity and duration were eliminated by analyzing only the data from those who did not know which drug they were taking. Since there are no data on the long-term toxicity of ascorbic acid when given in doses of 1 g or more per day, it is concluded that the minor benefits of questionable validity are not worth the potential risk, no matter how small that might be.


Persistent lymphocytosis with chromosomal evidence of malignancy. An inappropriate, sustained and absolute lymphocytosis in a young man was investigated using technics which attempted to define the more detailed features of these cells and their T and B subpopulations. The results of the tests for lymphocyte RFC (E) and complement (EAC) rosette formation, immunofluorescence, in vitro phytohemagglutin (PHA) stimulation and 14C-cyclo-phosphamide binding assays, when evaluated in a combined and interrelated fashion, indicated that the lymphocytosis was mainly but not solely, due to an absolute elevation in circulating T lymphocytes. Moreover, an aneuploid cell line with 47 chromosomes, presumably T cells, also was detected in PHA-stimulated cultures. These data, associated with the patient's anemia, lymphocyte-infiltrated bone marrow, hepatosplenomegaly, pharyngeal lymphoid tumor and the clonal proliferation of lymphocytes bearing an abnormal karyotype, furnish evidence that the lymphocytosis is more than an unremitting leukemoid reaction and is potentially neoplastic. The detection of the chromosomal abnormality at this patient's age and point in disease may make him especially unique in that he could be a clinical prototype for other patients with lymphoreticular tumors which remain undetected at their onset.


In vitro studies on human cervical epithelium, benign and neoplastic. The early neoplastic lesions of the cervix offer an excellent model to study the neoplastic process in the human; In vitro studies indicate that these lesions are intermediate between normal epithelium and invasive carcinoma in many aspects. More recent studies show that the in vitro cells retain many of the characteristics of their in vivo counterparts. The techniques are available for short-term culture of normal and CIN cells, but no cell lines have been established. Spontaneous transformation of normal cervical epithelial cells in culture has been rare, but planned transformation with chemical carcinogens and HSV-2 has not been successful. Even though much preliminary work has been done, the establishment of a cell line from the human cervix and methods for transforming normal cell in vitro are needed. Studies toward these objectives are continuing in this laboratory.


Histologic and nuclear grading and stromal reactions as indices for prognosis in ovarian cancer. Ovarian cancer is one of the most frustrating problems in gynecology. Each year about 14,000 new cases are diagnosed in the United States and almost 11,000 patients die from their ovarian cancer. The results from treatment are no better in 1973 than they were in the previous two decades; Early diagnosis is a matter of chance rather than a scientific method. Until early diagnosis can be made and treatment instituted with predictable promise for cure, attention must be directed to study the natural history of disease, its histologic and nuclear grading, as well as the stromal reaction of the cancer. This approach should further validate end results and, in the future, help improve the survival rate in ovarian carcinoma. With these criteria, 174 fresh cases were evaluated. The study showed that undifferentiated cancers were mainly in the unfavorable histologic and nuclear grades, while the better differentiated tumors were in the more favorable group. Mucinous cancers were characterized by the greatest number of tumors with favorable histologic and nuclear grades and generally had a better survival rate. Since the potency of tumors vary within a given stage, treatment should be tailored to the cancer rather than the stage of disease; In general, stage of disease was more important than histologic or nuclear grades in determining prognosis.


Ocular clinical findings and basement membrane changes in Goodpasture's syndrome. Goodpasture's syndrome is a rapidly progressive disease characterized by the onset of pulmonary hemorrhage with glomerulonephritis, leading to pulmonary and renal failure. The hallmark of this disease is linear deposition of antibasement membrane IgG in the basement membranes of the kidney and lung. In two cases of nonrhegmatogenous retinal detachment in patients with Goodpasture's syndrome, the first patient demonstrated multiple ischemic areas in the choroid on fluorescein angiography. Histopathologic and immunologic studies of the eyes in the second patient demonstrated macular edema and elevation of the retina in association with choroidal infarction and linear deposition of IgG in Burch's membrane and the basement membranes of the choroidal vessels.


Pseudorheumatoid nodules of the ocular adnexa. A clinicopathologic study of 21 cases revealed pseudorheumatoid subcutaneous nodules occurring in the eyelids and periorbital region of children and young adults. These nodules were most frequently located in the lateral upper eyelids and outer canthal region, and in five cases they were multiple. The lesions recurred in about 20% of the cases. In addition, new lesions located elsewhere were observed in 26% of cases. Histopathologically they resembled the subcutaneous nodules of rheumatoid arthritis and rheumatic fever. Follow-up information on 15 patients (from two to 12 years) and the results of laboratory studies on seven patients had failed to reveal any association with these two systemic diseases. Pseudorheumatoid nodules may be indicated when a healthy child or a young adult presents with solitary or multiple subcutaneous nodules, especially in the eyelids. These lesions pursued a benign clinical course and local excision, which is usually performed for diagnostic purposes, was the only treatment indicated. The lesions had a tendency to regress spontaneously; therefore, local recurrences should be treated conservatively by periodic follow-up examinations.


ABO Blood groups and corneal transplantation. A study of 150 corneal donor-recipient grafts, examined for ABO type, revealed that 25% of the grafts were from corneas from incompatible donors. Recipients with histocompatible sensitization exposures such as prior corneal transplant, one or more pregnancies, or one or more blood transfusions were no more likely to experience graft failure if the graft were from an ABO incompatible donor than from a compatible donor. Of 13 graft failures (8%), three of the failed grafts were from AB donors, a significant result. No detrimental effect of transplanting across the ABO barrier could be proven with assurance for any parameter.