Forceps operations in perspective. I. Midforceps rotation operations. Four hundred fifty-eight consecutive midforceps rotation operations were evaluated with a specially designed Perinatal Morbidity Index (PMI) and Maternal Morbidity Index (MMI). An unfavorable fetal outcome occurred in 30.8% of the midforceps rotation operations, and an unfavorable maternal outcome occurred in 13.5% of the cases. Twelve risk factors were found to be associated with suboptimal results. Among patients with no risk factors, an unfavorable fetal outcome occurred in 11% of the cases. Of the patients with three or more risk factors, in contrast, an unfavorable fetal outcome was found in 47% of the cases. A uniformly good fetal outcome was noted among patients selected as controls. Under ordinary circumstances, midforceps rotation operations should not be attempted in a patient already at significant risk. "Significant risk" is defined in the article.


Medical management of the sexually assaulted woman. Public concern about the sexual assault victim demands that the medical profession be better prepared to evaluate such patients. Modern guidelines for the medical evaluation and treatment of such victims are provided. A list of supplies for a "rape tray" and guidelines for obtaining laboratory tests are included. A detailed patient consent form and laboratory chain of evidence form will facilitate care. A plea is made for legislative support to pay for lab work and the establishment of state or national laboratories equipped to handle evidentiary material.


The utility and selection of laboratory tests in the diagnosis of the polycystic ovary syndrome. Fourteen patients with clinically diagnosed and surgically documented polycystic ovarian (Stein-Leventhal) disease (PCOD) and 16 normal control women were studied to identify the laboratory test or tests that, from the clinician's point of view, are most likely to aid in the nonsurgical diagnosis of the disease. A single random morning blood specimen was assayed in all cases for testosterone, epitestosterone, androstenedione, FSH and LH. The mean testosterone level for the PCOD patients was significantly greater (p less than 0.001) than that for the controls, with 50% of the patients showing elevated levels. Androstenedione showed a similar pattern, but mean epitestosterone levels were not significantly different from controls. FSH was not significantly different, but LH levels were significantly higher than controls (p less than 0.005), with 10 of 13 (77%) demonstrating elevated levels. A strong positive correlation was also found between the degree of virilization and the levels of LH, testosterone and androstenedione. This study suggests that the most useful diagnostic laboratory assay from a single drawing of blood is the serum LH; the only other useful test is testosterone and/or androstenedione. These data do not support other reports of elevated levels of epitestosterone or decreased values of FSH in PCOD.


Patient's sources of information on coitus during pregnancy. Obstetric patients were asked what sources they consulted for information about the advisability of coitus during pregnancy and what period of abstinence they inferred was proper from each. In general, the patients in the sample had incomplete information about these matters. A good indicator is that only 1 of the 17 patients in the sample had discussed them with her physician, and she did not know his recommendations.


Oligohydramnios and fatal pulmonary hypoplasia without amnion nodosum. Two cases of fatal pulmonary hypoplasia associated with hydrorrhea gravidarum are presented. Amnion nodosum was present in one case but not the other. The pathogenesis of amnion nodosum is reviewed, and the clinical implications of this pathologic finding are discussed in relation to whether the underlying pathology is renal agenesis or amniorrhea.


Granulocytic-like cells in the human fallopian tube. In the fallopian tube there are three main epithelial cell types, i.e., ciliated and nonciliated (or secretory) cells and intercalary, or peg, cells. An additional cell type has been considered either a wandering or a progenitor cell. Our morphologic and histochemical study shows a close similarity between a fourth cell type in the fallopian epithelium and the endometrial granulocytes (K cells). It is suggested that the two cells might be of an identical nature and that granulocytes could be ubiquitous in the entire Müllerian tract.


Chromosome aberrations in the mother and the newborn from drug-addiction pregnancies. Cytogenetic data were obtained prenatally and at delivery from 99 addicted pregnant women (80 from a methadone maintenance program and 19 heroin addicts) and their 101 offspring at delivery. About 10% of the 27,907 cells scored showed chromosomal aberrations. Chromosome damage was random and affected all chromosomes. There were no standard abnormal karyotypes. Apgar scores appeared to have some type of association with chromosome damage. In this study there were about 14 aberrations for every 10 aberrant cells scored.


Maternal intrauterine amine alterations in the pregnant drug addict. The pregnant drug addict has been a good study patient. Her neural hormonal value, as measured by urinary norepinephrine and epinephrine, is altered during pregnancy. The major difference between the antepartum state in the pregnant drug addict and that in the nonpregnant drug addict is hyperactivity of the adrenal gland. The intrauterine fetal homeostasis is altered by drug addiction in that the fetus is addicted, ted, as indicated by depressed amniotic fluid norepinephrine and epinephrine levels. If detoxification takes place, the fetus can respond in a dramatic fashion with increased levels of both norepinephrine and epinephrine. Detoxification is not recommended in the second and third trimesters of pregnancy because of the potential seriousness of these neural hormonal alterations.


A controlled trial of the theory of acupuncture in musculoskeletal pain. We carried out a randomized trail compraing acupuncture done is theoretically correct [appropriate] and incorrect [inappropirate] locations for chronic musculoskeletal pains in various sites. Throughout the trial, neither the patient, nor the assessor, nor the acupuncturist, knew if the site of the acupuncture was appropriate to the patient's symptoms according to acupuncture theory. Although 60% had reduced pain after three treatments, there was no significant difference between the treatments. Our findings, while not disproving the value of acupuncture, do not support the theory that certain specific points must be needled to relieve specific areas of pain.


NZB/WF1 hybrid autoimmune disease: a genetic analysis. This study analyzes the role of genetic and/or viral factors as etiologic agents in systemic lupus erythematosus in NZB/NZW F1 hybrid mouse, first by a backcross within the NZ strains. A separate study involved an outcross, production of an F2 generation, and then backcross to both NZ parents. The results were assayed by histologic evaluation of renal disease. Assay techniques for anti-DNA and proteinuria showed no evidence for segregation and were not useful. Histology of the kidney showed distinct segregation patterns consistent with the interpretation of the etiology as co-dominant genetic factors. While the virus[es] was not considered etiologic, mechanisms for relating activity to the pathogenesis were discussed.


Computer analysis of factors influencing the appearance of aseptic necrosis in patients with SLE. A computer analysis of 234 patients with SLE followed for an average of 31 months revealed 22 patients with aseptic necrosis of bone  (AN) (9%), with projected frequency approaching 30% at 10-15 years of follow-up. Most patients developed between four and seven years after diagnosis of SLE. When compared to all other patients with SLE and no AN or to three computer-selected groups matched by age of SLE diagnosis, duration of disease, or cumulative corticosteroid dose, AN did not correlate with any of the preliminary ARA criteria, total number of criteria fulfilled, renal disease, skin vasculitis, or disease activity. Although all patients received corticosteroid therapy prior to development of AN, no correlation was found with duration, peak dose, or cumulative dose of corticosteroid therapy.


Rheumatoid and normal synovial tissue in longterm culture. Evidence of cell heterogeneity and an approach to quantitation of of populations and the effect of passage. Longtern monolayer cultures of cells derived from explants of 21 normal and 31 rheumatoid synovial tissue specimens were studied and shown to be morphologically heterogeneous. The cultures were defined according to their cell size and their buoyant density as determined by separation on Ficoll density gradients. The investigations demonstrate that changes in these populations occurred with each passage of the cell lines. These findings emphasize the importance of using cultures of the same cultural age and passage for any comparative s tudy. The techniques described are useful for separating and defining the populations present in synovial tissue tissue cultures.


Ibuprofen, meningitis, and systemic lupus erythematosus. A 33 year old female with systemic lupus erythematosus developed an aseptic meningitis with a polymorphonuclear CSF pleocytosis temporally correlated with ibuprofen. Several weeks later after one ibuprofen tablet this syndrome recurred. This represents the second report of this unusual manifestation and suggest an adverse reaction to ibuprofen in SLE patients.


Synovial fluid eosinophilia following arthrography. A patient recovering from an acute gouty attack developed inflammation and eosinophilia of the synovial fluid following arthrography of the gouty joint. There was no evidence of systemic allergy to the contrast agent used. It is postulated that non-immune mechanisms were involved in the accumulation of eosinophils. An additional one of six synovial fluids obtained after arthrography contained 24% eosinophils. A review of the literature emphasizes the infrequency with which eosinophils are observed in synovial fluid.


Connective tissue activation. XII. Platelet abnormalities in patients with rheumatoid arthritis. Patients with rheumatoid arthritis frequently have an unexplained thrombocytosis which appears to be related to the severity of the disease process. This report shows that rheumatoid platelets have reduced saline soluble protein per 10(9) platelets, less of a lysosomal enzyme, acid phosphatase, and decreased connective tissue activating peptide (CTAP-III) activity. CTAP-III is a potent connective tissue mitogen, and promotes glycolysis and glycosaminoglycan synthesis, characteristics which make it an interesting candidate for a role as a mediator of inflammation.


Computerized tomography (body scan) of Baker's cyst. Computerized tomography (CT scan or body scan) has never been applied to the diagnosis of Baker's cysts. There cases of Baker's cyst evaluated by both CT scanning and arthrography are presented. The CT scan appears to be of no value.


Familial polyarticular osteochondritis dissecans masquerading as juvenile rheumatoid arthritis. A boy with polyarticular osteochondritis dissecans presented with clinical features of juvenile rheumatoid arthritis. Examination of the synovial fluid of an involved joint demonstrated inflammatory characteristics. Osteochondritis dissecans was present in the patient's mother and brother. Human leukocyte antigens HLA A-2, BW-15 and CW-4 were identified in the affected individuals.


Sigmoid volvulus in two patients with progressive systemic sclerosis. Sigmoid volvulus was diagnosed in two patients with progressive system sclerosis. In one case, this was initially confused with a high fecal impaction. Both cases responded to early surgical intervention. Sigmoid volvulus should be considered in the differential diagnosis of intestinal obstruction associated with progressive systemic sclerosis.


Septic arthritis associated with mycobacterium avium: a case report and literature review. A 58 year old man, with systemic lupus erythematosus, developed septic arthritis due to an atypical mycobacterium, M. avium. The patient's course, as well as 46 cases reviewed from the literature, illustrates the insidious nature of atypical mycobacterial infections. Septic arthritis or peri-arthritis was generally not suspected at initial evaluation, leading or at least 40% of patients receiving intra-articular steroids for non-specific reasons. A diagnosis was eventually obtained in 85% of cases by surgical biopsy and culture. In only15% was a diagnosis made by culture of synovial or bursal fluid. The relative in vitro resistance of "atypicals" to antituberculous drugs and the frequent necessity for surgery to make a diagnosis, led to surgery consituting partial or total therapy in 89% of cases. Whether patients were treated with surgery alone, surgery plus antituberculous drugs, or antituberculous drugs alone, clinical improvement generally occured. Because most patients had limited follow-up and because atypical mycobacterial infections often relapse, none of the cases reviewed should be considered "cures", be but rather instances of clinically inactive disease.


Talalgia. A review of 30 severe cases.

Talalgia. A review of 30 severe cases. Seronegative spondyloarthritides (Reiter's syndrome, ankylosing spondylitis, or  psoriatic arthritis) was diagnosed in 24 of 30 patients with severe heel pain. Most of the patients were carriers of the antigen HLA B27. Talalgia was frequently the first symptom of disease. Heel surgery is contra-indicated during the inflammation phase, since it may cause local aggravation and risk of ankylosis of the talocalcaneal articulation. Other causes of heel pain include tendon chondrocalcinosis, local tuberculous infection, and nodular tendinitis caused by a partial rupture of the tendon. On the other hand, severe talagia was rarely found in rheumatoid arthritis, and no case was related to the presence of tophi or xanthomas of the Achilles tendon.


Behçet's disease associated with a lymphoproliferative disorder, mixed cryoglobulinemia, and an immune complex mediated vasculitis. A woman, now 59 has been followed for 13 years with several manifestations of Behçet's disease. These were aphthous stomatitis, genital ulcers, uveitis causing blindness, recurrent erythema nodosum, and synovitis. In 1970 a poorly differentiated diffuse lymphocytic lymphoma appeared and was  treated with radiotherapy. In 1976 she developed a mixed cryoglobulinemia and an immune complex mediated vasculitis manifested by purpura and neuropathy which improved on prednisone and chlorambucil therapy. The subsequent course of her lymphoproliferative disorder suggest that it was in fact benign.


Erythema nodosum-arthopathy complex as an initial presentation of Behçet's disease. Report of five cases. In five males an erythema nodosum-arthropathy complex preceded the classical oro-genito-ocular triad of Behçet's disease by an average of 27 months. This symptom complex involving the legs initially suggested "idiopathic" erythema nodosum syndrome or acute sarcoidosis. As the diagnosis of Behçet's disease is clinical, these protean manifestations shoud be recognized as a possible "forme fruste" of the disease.


Studies on drug metabolism by use of isotopes. 23. Metabolic study of 1-butyryl-4-cinnamylpiperazine in the rat during development of tolerance by using two kinds of deuterium-labeled forms. Mass fragmentographic determination of the plasma, brain, and liver levels of 1-butyryl-4-cinnamylpiperazine (I) and its metabolites in tolerant and nontolerant rats was carried out by using two kinds of deuterium-labeled compounds. 1-Butyryl-4-[a-d2]cinnamylpiperazine (I-d2) was used to develop tolerance and 1-butyryl-4-[arom-d5]cinnamylpiperazine (I-d5) to clarify the metabolic fate of I after I-d2 administration. The present method allowed the clarification of the metabolism of I-d2 and I-d5 independently. In tolerant rats, the brain and liver were lower for I-d5 and higher for I-d5 metabolites than in nontolerant rats. There was no significant difference in the plasma levels of I-D5 between tolerant and nontolerant rats. Our data seem to suggest that development of tolerance to I results from a more rapid metabolism of the drug due to hepatic enzyme induction.


Piperazinylpyrazines with central serotoninmimetic activity. A series of 2-(1-piperazinyl)pyrazines was synthesized and evaluated for central serotonin-like activity. The most interesting member of the series, 6-chloro-2(1-piperazinyl)pyrazine (3a), had pharmacological properties characteristic of potent central serotoninmimetic activity and only weak peripheral serotoninmimetic action. Structural similarities between 3a and serotonin are discussed.


Oxidative and cardiovascular studies on natural and synthetic catecholamines. The cyclic voltammometric behavior of epinephrine, norepinephrine, dopamine, epinine, alpha-methyldopamine, beta-methyldopamine, beta-methylepinine, and beta-methoxyepinine has been examined in order to evaluate substituent effects on cyclization rates of the electrochemically generated quinones. We observed that alpha and beta substituents caused a modest enhancement of cyclization rates while an N-methyl group dramatically increased cyclization rates. No correlation was observed between calculated amine pKa values, suggesting that differences in cyclization rates between the primary and secondary amine series were due to inherent nucleophilicity, a measure of which would be gas-phase proton affinities. The acute pressor effects of the newly synthesized catecholamines were compared with the native amines.


Effects of deuteration on locomotor activity of amphetamine. The synthesis of fully deuterated amphetamine (phenyl-2-aminopropane-d11) in which 11 deuterium atoms are bonded to carbons and two other highly deuterated analogues is described. Their toxicities and in vivo spontaneous locomotor activities in mice were examined and compared with that of the parent protioamphetamine. A significant reduction in toxicities and a decrease in spontaneous locomotor activity were observed for these highly enriched deuterated analogues, as compared to protioamphetamine.


Antitumor 1-(X-aryl)-3,3-dialkyltriazenes. 1. Quantitative structure-activity relationships vs. L1210 leukemia in mice. Quantitative structure-activity relationships (QSAR) have been formulated for phenyl-, pyrazolyl-, and imidazolyltriazenes acting L1210 leukemia in mice. All three sets of congeners have the same ideal lipophilicity (log Po approximately 1). Electron releasing substituents increase potency; ortho substitution decreases activity. The synthesis of a number of new triazenes and some of their partition coefficients are reported.


Antitumor 1-(X-aryl)-3,3-dialkyltriazenes. 2. On the role of correlation analysis in decision making in drug modification. Toxicity quantitative structure-activity relationships of 1-(X-phenyl)-3,3-dialkyltriazenes in mice. A series of 11 triazenes (X-C6H4N=NNRCH3) was characterized for toxicity in mice (LD50). The quantitative structure-activity relationship (QSAR) obtained for toxicity was compared with the QSAR for antitumor activity. The close correspondence of the two QSAR leaves essentially no means for the synthesis of more potent, less toxic triazenes.


Cytostatic quinones. 3. Synthesis of benzotriazolequinones by a new oxidation with m-chloroperbenzoic acid. Biochemical studies. Oxidation of N-1 and N-2 alkylbenzotriazoles with m-chloroperbenzoic acid afforded 1-alkylbenzotriazole 3-oxides and 2-alkylbenzotriazole-4,4-diones, respectively. The quinonic compounds inhibited the "in vitro" growth of both HeLa and KB cells, the synthesis of macromolecules (DNA, RNA, and proteins), and the uptake of glucose by Ehrlich carcinoma ascites cells. A possible mode of action is suggested.


Aroyl- and arylisoquinolineacetic acids as antiinflammatory agents. A series of 1-benzoyl- and 1-phenylisoquinolineacetic acid derivatives was prepared and tested for antiinflammatory activity. The most potent compound synthesized, 1-(4-chlorophenyl)-3-isoquinolineacetamide, was as active as phenylbutazone in the Evans blue carrageenan-induced pleural effusion assay but inactive in the adjuvant-induced arthritis model of chronic inflammation.


Synthesis of spiro[tetralin-2,2'-pyrrolidine] and spiro[indan-2,2'-pyrrolidine] derivatives as potential analgesics. Spiro[tetralin-2,2'-pyrrolidine] (13) and spiro[6-methoxytetralin-2,2'-pyrrolidine] (17) were prepared by initial Michael condensation of 2-nitrotetralin and 6-methoxy-2-nitrotetralin, respectively, with methyl acrylate to give 7 and 8, both of which could be reductively cyclized to 10 and 11, followed by LiAlH4 reduction. Spiro[indan-2,2'-pyrrolidine] (15) was prepared in an analogous manner form 2-nitroindan, and spiro[6-hydroxytetralin-2,2'-pyrrolidine] (19) was prepared by O-demethylation of 17. Compound 13 and its N-methyl derivative, 14, both showed good analgesic activity. Compounds 13-16 all possessed weak antidepressant properties, but neither 19 nor its N-methyl derivative 20 had any significant CNS activity.


Antibacterial activity of N-(beta-styryl) formamides related to tuberin. A series of para-substituted N-(beta-styryl)formamides, analogues of tuberin (4a), has been prepared and assayed for antibacterial activity. The methylthio, ethoxy, and methyl analogues 4e, 4j, and 4t were about twice as active as tuberin against Mycobacterium phlei. Although tuberin lacks activity against Staphylococcus aureus, several of the analogues described were found to inhibit this organism. The phenyl group of tuberin is not a prerequisite for activity since analogues based on naphthyl or ferrocenyl groups were also active. A quantitative structure-activity relationship further implied that an aromatic group need not be present, suggesting the synthesis of the cyclohexyl and n-amyl analogues which were found to possess high activity.


Syntheses and uncoupling activities of alkyl dithiocarbazates and alkyl pyridinecarbonyldithiocarbazates. A series of alkyl dithiocarbazates, alkyl 3-picolinoyldithiocarbazates, alkyl 3-nicotinoyldithiocarbazates, alkyl 3-isonicotinoyldithiocarbazates, and alkyl 3-picolinoyl-2-methyldithiocarbazates was prepared. These alkyl pyridinecarbonyldithiocarbazates were shown to be uncouplers of oxidative phosphorylation in mitochondria. The finding that uncoupling activity increased with increase in the length of the alkyl chains of the compounds indicates that hydrophobicity influences the activity. The nonyl derivatives had the highest activity. The results also suggested that a dissociable acidic proton is necessary for the uncoupling activity.


Diarylamidine derivatives with one or both of the aryl moieties consisting of an indole or indole-like ring. Inhibitors of arginine-specific esteroproteases. A series of 62 diarylamidine derivatives was evaluated for their antiproteolytic activity. In all but two of the compounds one or both of the amidino-substituted aryl moieties was either an indole or an indole-like ring. The latter included indene, benzimidazole, benzofuran, benzol[beta]thiophene, and several other related nitrogen-containing heterocycles. Several of the compounds exhibited considerable inhibitory potency against thrombin, trypsin, and pancreatic kallikrein. An outstanding inhibitor of trypsin was found in bis(5-amidino-2-benzimidazolyl)methane (compound 42) with a Ki value of 1.7 X 10(-8) M(pH. 8.1, 37 degrees C). Another derivative, 1,2-di(4-amidino-2-benzofuranyl)ethane (compound 21), proved to be a highly effective inhibitor of the overall blood clotting process. From a general structure-activity standpoint these compounds demonstrate that minor structural variations of low-molecular-weight inhibitors can result in significant changes in specificity and potency with regard to antiproteolytic activity.


Synthesis and antiinflammatory activity of trisubstituted pyrimidines and triazines. A series of mono-, bi-, and tricyclic pyrimidines and as-triazines was prepared and their antiinflammatory activity measured against carrageenan-induced edema in the rat. The more active analogues (ED50), including 4-pyri-dylpyrimidines 4a (38), 4b (47), and 4g (49) and 2-hydroxypyrimidine 8r (43), were then tested against adjuvant-induced edema in the rat. None was active in the adjuvant arthritis model.


Nonsteroidal antiinflammatory agents. 2. Derivatives/analogues of dibenz[b,e]oxepin-3-acetic acid. 6,11-Dhydro-11-oxodibenz[b,e]oxepins and some related compounds have been synthesized and evaluated for antiinflammatory effect according to the carrageenan paw edema method in rats. The structure-activity relationships have been discussed among acetic acid, carboxylic acid, alcohol, and tetrazole derivatives of dibenzoxepins and acetic acid derivatives of thienobenzoxepins and of the corresponding thiepins. The 3-isopropyl alcohol 9 and 11-deoxo-3-propionic acid (49) were more active than indomethacin but not as active as the title compound (i.e., 43). Carboxylic acids, tetrazoles, esters, amides, and ketones were less active than the corresponding acetic acids. Three compounds (31, 33, and 34) were evaluated for ulcerogenicity and lethality but none surpassed 6,11-dihydro-11-oxodibenz[b,e]oxepin-3-acetic acid (41) in therapeutic ratio.


Anionic polymers and biological activities. Effects of some new polycarboxylic acids on the ascitic sarcoma 180 in mice. Eleven new polymeric carboxylic acids with widely different solubilities in water have been synthesized. The activities of these polymers against the ascitic sarcoma 180 tumor of mice and their acute toxicities in mice have been compared with molecular parameters of the polymers such as molecular weights, charge densities, and abilities to complex calcium and magnesium ions. The maximum effectiveness of these polymers against ascitic sarcoma 180 of mice is greatest for those polymers having fewer carboxyl groups ionized at pH 7. Toxicities are lower for polymers having more carboxyl groups ionized at pH 7.


Synthesis and antiallergic activity of some mono- and disubstituted xanthone-2-carboxylic acids. A series of xanthone-2-carboxylic acids, substituted mainly with electron-withdrawing groups, has been synthesized and assayed for antiallergic activity, using the passive cutaneous anaphylaxis (PCA) reaction in the rat. The effect of substituent type and substitution pattern on PCA neutralizing capacity is presented.


An ab initio study of electronic factors in metabolic hydroxylation of aliphatic carbon atoms. The monooxygenase-mediated hydroxylations of aliphatic carbon atoms are known to be regioselective for positions alpha to heteroatoms or to pi systems (aromatic rings, carbon-carbon double bonds, carbonyl groups). Ab initio calculations (STO-3G and in some cases 4-31G) were performed on model molecules, indicating that the Mulliken overlap populations (taken as indices of electron bond densities) of Calpha-H bonds being regioselectively hydroxylated are larger than Cbeta-H and Cgamma-H overlap populations. These results support the hypothesis that metabolic C-hydroxylations occur by insertion of an activated oxygen species of electrophilic nature, probably oxene.


Electronic structures of some antimicrobial N-chloramines. Possible existence of intramolecular hydrogen bonding and its effect on germicidal efficiency. The photoelectron spectra of eight N-chloramines and N,N-dichloramines derived from either alpha-aminoisobutyric acid or 2-amino-2-methylpropanol have been measured. The lone-pair ionization potentials obtained from the photoelectron spectra have been interpreted to indicate that a substantial intramolecular interaction exists between tne N-H function and the various oxygen lone pairs of the N-chloramines. Such an intramolecular interaction for the N-chloramines can explain at least in part why these molecules are less potent as antimicrobial agents than are the N,N-cichloramine analogues for which a similar intramolecular interaction is impossible.


Steroid antifertility agents. Ionic complexes of basic derivatives for prolonged action. Ethynylestradiol 3-dimethylaminopropionate (1), norethindrone 3-(O-dimethylaminopropyl)oxime (syn and anti isomers, 2a and 2b), and testosterone 3-(O-dimethylaminopropyl)oxime (3) have been prepared and converted to zinc and aluminum tannate complexes as potentially long-acting prodrug forms of the parent steroids. The basic derivatives and the complexes showed the appropriate hormonal activities although they were less active in acute tests than the respective parents. The complexes of 1 showed prolonged activities and, in particular, the zinc tannate showed a prolonged duration of antifertility activity in the rat on subcutaneous administration in an aluminum monostearate gel.


Solution conformations of muscarine and some analogue. Proton magnetic spectra have been recorded for muscarine and two biologically active cyclopentane analogues. In order to observe homonuclear intramolecular nuclear Overhauser effects, the -N+(CH3)3 signal was irradiated and increases in integrated intensities for other key signals in the molecule were observed. The results indicate that the quaternary side chain in these compounds is in an extended conformation in aqueous solution.


The 'no lose' philosophy in medicine.

The 'no lose' philosophy in medicine. This article as the series title suggests focuses our attention on decisions, both medical and ethical, which face doctors and related personnel in the medical profession daily. Many of these decisions take the form of a choice to one thing or another without being very sure of the outcome of either action. Mr Galbraith explores the pros and cons of what he calls the 'no lose' philosophy in medicine and which plays a large part in medical decision making. He concludes that possibly we may need a new philosophy rather than continuing to use more and more of our resources on care, which is perhaps being carried out as a means of avoiding making value judgements and thus possibly, prevents us from solving some of today's difficult ethical problems.


Incest.

Incest. This paper is based on two presentations under the auspices of thf Edinburgh Medical Group in 1976. Dr Noble and Professor Mason, explore the incidence of incest and society's attitudes to it from legal, anthropological, medical and social viewpoints. They place this in a world context by looking at the universal prohibition of incest and the theories related to that taboo. In conclusion, they suggest that there seem to be sufficient sensible grounds on which to base a reappraisal of attitudes to incest. Their conclusions are in turn appraised by brief commentaries from a moral philospher and a psychiatrist.


Declaration of Hawaii.

Declaration of Hawaii. We are printing in full the text of the Declaration of Hawaii, a Code of Ethics adapted by the World Psychiatric Association at its meeting in Honolulu in August 1977. The text is followed by a brief commentary from Dr Clarence Blomquist, the person responsible for drawing up the draft code. Dr Blomquist argues that the main function of a code of this kind is to supply general guidelines which will alert psychiatrists to the ethical problems and moral traps of their profession.


Political neutrality and international cooperation in medicine. International cooperation is an integral part of furthering medical and scientific progress. Many specilist societies exist for that purpose and have written into their constitutions that such cooperation and coordination is their aim. They hope to achieve their aims by exchange, in all languages, of information and by so doing strengthen the relations between individual physicians and scentists as well as between corporate professional bodies from different countries.  However, at the same time emphasis is laid on the political neutrality of such organsations. Increasingly, this 'neutrality' is being questioned as doctors and scientists become aware of abuse and distortion of their profession taking place in other countries. H Merskey highlights the problems and offers his opinion on the ethics of maintaining these professional relationships with colleagues abroad who are involved in such abuse and distortion.


When consent is unbearable--a case report. Informed consent has become one of the central problems in medical ehtics. At first sight, it would seem that no argument can be made against a person's right to be fully aware of the extent, course, and implications of his medical condition. It seems equally obvious that it is the patient's right to participate in, influence, or fully and solely assume the decisions of medical actions that should be undertaken or withheld with regard to his disease. Nevertheless, there are circumstances in which these commonly held assumptions about a patient's rights may not apply. It is the purpose of this report to describe a case where informed consent was deliverately not sought, and to discuss the ethical issues involved.


Testing new drugs--the human volunteer.

Testing new drugs--the human volunteer. Professor Duncan Vere lays before us the idealised guidelines used for recruiting volunteers on which to try and test new medicines. He points out that if these were followed rigidly, few, if any volunteers would be found for this vital work. Inducements are used, but the size of these determines whether society deems it right or wrong. However, the aim is to help and advise volunteers of the need for such tests and the risks involved and therefore the information leaflet reprinted as part of the article indicates how the drug testers are attempting to encourage volunteers in as ethical a way as possible. To abandon human tests with new drugs may be unethical. A balance is sought.


Teaching medical ethics: University of Nijmegen, The Netherlands. During his internship the medical student often feels a basic need for ethical discussion. The department of medical ethics at the University of Nijmegen offers a monthly discussion in single clinical departments. The ethicist is then assisted by staff responsible for guiding the interns. These discussions, based on daily experience, aim at critical evaluation of ways the profession is being exercised. As such they form an essential counterpart to the more theoretical learning in classrooms and seminars during previous years. The method is rather flexible. Either an inventory of problems is made, followed by a selection and discussion of one problem. Or a discussion is initiated by an introduction by either staff or ethicist. The actual programme and its origin, the objectives and some of the problems of such a programme are presented in this article.


Lesbian couples: should help extend to AID? A considerable amount of publicity has recently centred on a few Lesbian couples who have successfully obtained artificial insemination by donor (AID) in order to have a child. Advice was orginally sought on a private basis from the Journal on the following case: now the issue is public knowledge, the doctor presenting the case has agreed to open discussion, and a case conference was convened to consider it. Those taking part were: Jackie Forster, Co-editor of Sappho; lesbian feminist magazine; Carola Haigh, General Practitioner, London; Ian Kennedy, Barrister and Lecturer in Law, Kings College, London; Anthony Parsons, Gynaecology Department, Kings College Hospital, London; Jennifer Pietroni, General Practitioner, London; Gordon Price, Department of Child & Family Psychiatry, Kings College Hospital, London; Rose Robertson, from Parents Enquiry, a counselling organisation for families where there is an incidence of Homosexuality and where it is causing stress. Roger Higgs, General Practitioner and organiser of the Case Conference Series, was in the Chair.


Hereditary pancreatitis in England and Wales. Information from 72 patients from 7 families in England and Wales confirms that hereditary pancreatitis is inherited as an autosomal dominant conditions with limited penetrance. The degree of penetrance is approximately 80%. These patients have had recurrent attacks of abdominal pain starting from childhood or young adult life. The mean age of onset in the 7 families studied was 13.6 years. There were two peaks, with maximum numbers at 5 years and 17 years. The second peak was thought to represent genetically susceptible individuals having pain brought on by alcohol rather than representing evidence of genetic heterogeneity. Five of the 7 families had members with both childhood and adult ages of onset. Only 4 patients out of 72 had life-threatening disease and in the majority of cases the attacks of pain were of nuisance value only. Hereditary pancreatitis was implicated in only 1 patient's death and this was not definite. Patients appear to get better after a period of symptoms usually as they approach middle age, or after a severe attack. In older patients alcohol, emotional upsets, and fatty food appear to precipitate attacks. Pancreatic insufficiency (5.5%), diabetes mellitus (12.5%), pseudocysts (5.5%), and haemorrhagic pleural effusion are uncommon complications. Portal vein thrombosis occurred definitely in 2 patients and was suspected in 3 others. Carcinoma of the pancreas was not found in any of 72 patients studied in detail; however, 2 members from a family not visited personally had chronic pancreatitis and malabsorption going on to carcinoma. They may have suffered from a different disease. Genetic linkage information was too slight for many definite conclusions. However, there was no suggestion of linkage with any of the markers tested.


First premarital screening of thalassaemia carriers in intermediate schools in Latium. In the 1975 to 1976 school year, under the auspices of the Health Authorities of the Latium Region, the Rome Microcythaemia Centre carried out for the first time a partial screening survey of thalassaemia carriers among the students of the compulsory intermediate school in Latium. This work was the beginning of a new preventive school health service aimed at the prophylaxis of Cooley's disease. In 23 places investigated in Latium, 17724 students were examined, 13354 of whom were in Rome and 4370 elsewhere. The mean percentage of co-operation was 70% and the mean percentage of thalassaemia 2.42%. Thalassaemic students were invited to attend the centre for a check-up along with their families: about half had already come in by the end of June 1976. All students examined, whether normal or thalassaemic, have received written results of the tests. The screening survey aroused notable interest and obtained wide approval both at school and at home. The news of being thalassaemia carriers, even if not welcome, was never the cause of family tragedy.


Brachydactyly, distal symphalangism, scoliosis, tall stature, and club feet: a new syndrome. Five members of a kindred with brachydactyly and distal symphalangism, normal stature, pes cavus, and scoliosis were ascertained. The pedigree was consistent with autosomal dominant inheritance. The combination of clinical and radiological features is believed to be distinct from those previously reported in patients with brachydactyly/symphalangism.


Linkage studies in Van der Woude syndrome. A newly ascertained kindred segregating Van der Woude syndrome through four generations is described. Linkage studies using the methods of Ott (1974) were carried out using 19 marker loci.


Nephrogenic diabetes insipidus and Werdnig-Hoffmann disease in a child: an unusual association. The unusual association of Werdnig-Hoffmann disease and nephrogenic diabetes insipidus in a 5-month-old child is described for the first time. The association is casual, considering the different pathways of genetical transmission in these two diseases. The possibility of identifying the heterozygote is discussed and it appears to be limited to nephrogenic diabetes insipidus.


Necropsy of original case of Lowry's syndrome. The necropsy findings are reported on one of the original sibs of Lowry's syndrome. The child, who died at 7 years of bronchopneumonia, was severely dwarfed, microcephalic, and microphthalmic. The brain was small and extensively calcified, the cerebellar cortex hypoplastic, and the retinae atrophic. There were multiple skeletal and integumental and minor renal abnormalities. The lymphoid tissue was much reduced, and many arteries and arterioles were thickened and narrowed. This constitutes a unique constellation of lesions.


Late discovery of a case of testicular feminisation. The accidental discovery, in an inguinal hernia, of a male gonad in a 67-year-old woman is reported. The association of an unambiguous female phenotype with a purely male karyotype and a male gonad suggests the diagnosis of testicular feminisation. The differential diagnosis, particularly of testicular feminisation with true hermaphroditism, is discussed.


Inconsistent expression of both centromeres of a dicentric Y chromosome in a child with ambiguous external genitalia. A newborn child with ambiguous external genitalia had evidence of internal female development on the left and internal male development on the right. Blood chromosome analysis showed three cell types: 45,X; 46,XY with the Y being submetacentric and about twice the usual size with two 'centromeric' C bands; and 46,X,dic(Y). Chromosome studies from the skin, uterus, and Fallopian tube showed almost exclusively 45,X cells. This represents the second reported patient in whom two centromeres are inconsistently expressed though present as shown by two 'centromeric' C bands.


Deletion 14q and pericentric inversion 14. A woman with deletion 14q as well as inversion 14 is presented, and physical signs are compared with those of patients with deletion long arm 13. No previous case of deletion long arm 14 has been published.


Meckel's syndrome (dysencephalia splanchno-cystica) in two Pakistani sibs. A Pakistani couple, who were first cousins once removed through their fathers, and whose mothers were also related, had two liveborn children, a boy and a girl. Both children died within 2 hours of birth with occipital encephalocele, microcephaly, polycystic kidneys, and cystic distension of intrahepatic bile ducts. Both children had normal karyotypes. These abnormalities constitute Meckel's syndrome (dysencephalia splanchno-cystica); this is the fifth report of parental consanguinity, adding further support to the evidence for autosomal recessive inheritance of the disorder.


Health professions education and public policy: a research agenda. The Work Group on the Education of the Health Professions and the Nation's Health offers the theme of discontinuity to describe who so little useful knowledge has been derived from research in this area and to suggest a more productive approach for future studies. Discontinuities are evident amoung the needs of patients and populations and how professionals practice what is taught in professional schools. The work group recommends seven areas for study in the expectation that new information might alleviate these discontinuities.


First-year graduate medical education positions obtained by U.S. graduates in 1977. When the 2,308 residencies obtained by U.S. medical school graduates outisde of th National Intern and Resident Matching Program were added to those of the 11,172 students who matched, the distribution of all 1977 graduates among specialties was found to be essentially the same as for those who matched, but regional differences were marked. A regional comparison of the location of the residencies obtained by the graduates with the location of the schools attended by students suggested that recruitment of graduates from other regions was as important in determining the number of first-year residents as was retention of graduates in a given region.


Experience with college of medicine departmental reviews. Departmental review are a means of assessing quality in administrative and academic functions. Policies and guidelines have been established. The review processes are time consuming and costly. However, the goals for such reviews are achievable. Guidance to improve department head performance is provided, and search for new leadership when indicated is enhanced.


A systematic comparison of teaching hospital and remote-site clinical education. This paper present a methodology for examining activities of medical students on multisite clinical clerkships to determine whether differences exist in the educational experience offered at various sites. Five criterion variables are explored: distribution of student activities, type or class of clinical conditions encountered by students, degree of "esoterism" of those conditions, type of student role, and flexibility of student role. A format for data collection, employing a specially designed activity recording pad, was developed as part of the study. Application of this method to a clerkship in obstetrics and gynecology documents the existence of systematic differences in the educational experiences offered at different sites, particularly with regard to type of activities undertaken and conditions encountered. Most notably, the results suggest that it is fallacious to dichotomize clerkship sites as "academic" or "community" based. It is found that community hospitals themselves can differ markedly and offer an experience paralleling that of the academic referral center.


The experiment in medical education at the City College of New York. Described is a program leading to the B.S. and M.D. degrees in six or seven years which integrates the physical sciences with the basic medical sciences and emphasizes the humanities and social sciences as a necessary component of the physician's education. The selection process is designed to identify young men and women who will become primary care physicians in underserved urban communities. At the end of the fourth year it was shown that the graduates were comparable with second-year medical students as measured by national examinations. It is suggested that the changes made in the premedical curriculum merit general consideration inasmuch as the course work is more pertinent to the practive of medicine and offers a sound education for other health careers for those unable to continue their medical training.


U.S. medical students in Nepal.

U.S. medical students in Nepal. A formal course in Human Ecology in the Himalayas proved to be a powerful educational innovation partly because of its international setting. The six students in the medical part of this course experienced a profound affective impact on their career goals, a totally new orientation toward the problems of poverty in the United States, and a changed appreciation of the need for preventive measures and a community approach. The effect was far greater than that usually associated with individualized international experiences because of careful preparatory seminars, group activities which included surveys and research, and abundant opportunity for interpretive discussions as cultural and health care shock was being experienced. Clinical work was kept in perspective and provided opportunities for learning, not only about exotic diseases but also about what could be done under the simplest of conditions.


Perioperative diabetic consultation: a plead for improved training. To determine the clinical and educational impact of an academic general internal medicine consultation service, the investigators selected as a model the perioperative management of diabetes mellitus. They analyzed 17 consultative episodes over two years by retrospective medical record review to identify patterns and shortcomings. Most patients were elderly black females with maturity-onset diabetes mellitus exhibiting numerous past diabetic complications and other active general medical problems. Major findings included common failure to define the consultation purpose or document adequately follow-up visits, incomplete professional adherence to published guidelines for perioperative diabetic management, and correlation between failure to document the consultant's own physical examination and failure to reach new conclusions. Median cost for consultant-recommended tests was $179 (range $82 to $552) without clear linkage between medical care process and outcome. Consultative skills must be taught more effectively if medical consultations are to have maximal impact.


Fusion of secretory vesicles isolated from rat liver. Secretory vesicles isolated from rat liver were found to fuse after exposure to Ca2+. Vesicle fusion is characterized by the occurrence of twinned vesicles with a continuous cleavage plane between two vesicles in freeze-fracture electron microscopy. The number of fused vesicles increases with increasing Ca2+-concentrations and is half maximal around 10(-6)M. Other divalent cations (Ba2+, Sr2+, and Mg2+) were ineffective. Mg2+ inhibits Ca2+-induced fusion. Therefore, the fusion of secretory vesicles in vitro is Ca2+ specific and exhibits properties similar to the exocytotic process of various secretory cells. Various substances affecting secretion in vivo (microtubular inhibitors, local anesthetics, ionophores) were tested for their effect on membrane fusion in our system. The fusion of isolated secretory vesicles from liver was found to differ from that of pure phospholipid membranes in its temperature dependence, in its much lower requirement for Ca2+, and in its Ca2+-specificity. Chemical and enzymatic modifcations of the vesicle membrane indicate that glycoproteins may account for these differences.


Effect of aldosterone on incorporation of amino acids into renal medullary proteins. Studies on the effects of pretreatment with aldosterone on the incorporation of 3H leucine or 3H methionine into proteins in renal slices were carried out in Joklik-modified minimal essential medium. Administration of aldosterone (2microgram/100 g body wt) to adrenalectomized rats increased 3H leucine incorporation into trichloroacetic acid insoluble fractions of crude homogenates of cortical slices by 15.5 +/- 0.4% and of medullary slices by 53.5 +/- 1.3%. No increase in isotope incorporation was observed in slices of renal papilla or spleen prepared from the same rats. Aldosterone had no effect on the 3H-leucine content of the trichloroacetic acid-soluble fractions of all three renal zones and the spleen. The dose of aldosterone that elicited a half-maximal increase in 3H-methionine incorporation into proteins of renal medullary slices (0.45 microgram of aldosterone/100 g body wt) was indistinguishable from that needed to elicit a halt-maximal increase in the urinary K+/Na+ ratio (0.35 microgram of aldosterone/100 g body wt). Dexamethasone, a potent glucocorticoid, at a dose of 0.8 microgram/100 g body wt did not augment 3H-leucine incorporation into renal medullary proteins but was effective at 8 microgram/100 g body wt. Spirolactone (SC-26304), a potent anti-mineralocorticoid, abolished the effect of aldosterone on amino acid incorporation into medullary proteins when administered at a 100-fold higher dosage [i.e., 80 microgram (per 100 g body wt)]. These results imply that the action of aldosterone on amino acid incorporation is mediated by the mineralocorticoid rather than the glucocorticoid pathway, presumably the mineralocorticoid receptors. Moreover, pretreatment of the rats with actinomycin D (70--80 microgram/100 g body wt) erased the effect of aldosterone (0.8 microgram/100 g body wt) on amino acid incorporation into medullary proteins. In paired experiments with 3H and 35S methionine, aldosterone (0.8 microgram/100 g body wt) increased methionine incorporation into trichloroacetic acid precipitable proteins of subcellular fractions of the renal medulla. The effect of aldosterone on incorporation of methionine into medullary cytosol proteins was analyzed further by polyacrylamide gel electrophoresis at pH 8.3 in tris-glycine buffer. The gel profiles indicate that aldosterone significantly increased methionine incorporation into at least one protein (independent of the isotope) with a molecular weight of approximately 31,000. This increase was inhibited by either pretreatment of the rat with actinomycin D (70--80 microgram/100 g body wt or SC-26304 (80 microgram/100 g body wt). Dexamethasone (0.8 microgram/100 g body wt) did not increase incorporation of methinine into the medullary cytosol proteins resolved by polyacrylamide gel electrophoresis.


Effects of amphotericin b on the electrical properties of Necturus gallbladder: intracellular microelectrode studies. Intracellular microelectrode techniques were employed to study the mechanism by which amphotericin B induces a transient mucosa-negative transepithelial potential (deltaVms) in the gallbladder of Necturus. When the tissue was incubated in standard Na-Ringer's solution, the antibiotic reduced the apical membrane potential by about 40 mV, and the basolateral membrane potential by about 35 mV, whereas the transepithelial potential increased by about 5 mV. The electrical resistance of the apical membrane fell by 83%, and that of the basolateral membrane by 40%; the paracellular resistance remained unchanged. Circuit analysis indicated that the equivalent electromotive forces of the apical and basolateral membranes fell by 35 and 11 mV, respectively. Changes in potentials and resistances produced by ionic substitutions in the mucosal bathing medium showed that amphotericin B produces a nonselective increase in apical membrane small monovalent cation conductance (K, Na, Li). In the presence of Na-Ringer's on the mucosal side, this resulted in a reduction of the K permselectivity of the membrane, and thus in a fall of its equivalent emf. During short term exposure to amphotericin B, PNa/PCl across the paracellular pathway did not change significantly, whereas PK/PNa doubled. These results indicate that deltaVms is due to an increase of gNa across the luminal membranes of the epithelial cells (Cremaschi et al., 1977. J. Membrane Biol. 34:55); the data do not support the alternative hypothesis (Rose & Nahrwold, 1976. J. Membrane Biol 29:1) that deltaVms results from a reduction in shunt PNa/PCl acting in combination with a rheogenic basolateral Na pump.


Kinetic analysis of the inhibition of sulfate transport in human red blood cells by isothiocyanates. A kinetic analysis of anion self-exchange in human red blood cells, in the presence of an irreversible inhibitor, is presented and applied to the study of the inactivation of sulfate transport by three isothiocyanates: 3-isothiocyano-1,5-naphthalenedisulfonic acid, disodium salt (INDS), 1-isothiocyano-4-naphthalene sulfonic acid, sodium salt, monohydrate (INS), and 1-isothiocyano-4-benzenesulfonic acid, sodium salt, monohydrate (IBS). The time dependence of the inhibition of sulfate transport by the isothiocyanates used could be described by a single exponential and could be shown to contain a reversible and an irreversible component. In each case a portion of sulfate efflux was found to be resistant to inactivation. The residual portion of the sulfate efflux varied with inhibitor: 4% for INS, 16% for INDS, and 34% for IBS. INS showed the largest reversible inhibitory effect (12% of the flux remaining at 0.2 mM inhibitor concentration), while INDS showed the weakest effect (92% of the flux remaining at 0.3 mM inhibitor concentration). IBS had the highest rate of inactivation while INDS had the lowest. The kinetic analysis further suggests that all three isothiocyanates bind reversibly to an inhibitory site on the membrane before they bind covalently, and therefore irreversibly, to the same site on the membrane. The equilibrium constant for the dissociation of the reversibly-bound complex, Ki, and the rate of irreversible inactivation after all membrane sites are reversibly bound, kmax, have been computed for all three inhibitors: INDS (Ki = 420 micron, kmax = 5.04 hr-1), INS (Ki = 148 micron, kmax = 6.48 hr-1), and IBS (Ki = 208 micron, k(max) = 8.11 hr-1).


Basolateral membrane potential of a tight epithelium: ionic diffusion and electrogenic pumps. The contribution of specific ions to the conductance and potential of the basolateral membrane of the rabbit urinary bladder has been studied with both conventional and ion-specific microelectrode techniques. In addition, the possibility of an electrogenic active transport process located at the basolateral membrane was studied using the polyene antibiotic nystatin. The effect of ion-specific microelectrode impalement damage on intracellular ion activities was examined and a criterion set for acceptance or rejection of intracellular activity measurements. Using this criterion, we found (K+) = 72 mM and (Cl-) = 15.8 mM. Cl- but not K+ was in electrochemical equilibrium across the basolateral membrane. The selective permeability of the basolateral membrane was measured using microelectrodes, and the data analyzed using the Goldman, Hodgkin-Katz equation. The sodium to potassium permeability ratio (PNa/PK) was 0.044, and the chloride to potassium permeability ratio (PCl/PK) was 1.17. Since K+ was not in electrochemical equilibrium, intracellular (K+) is maintained by active metabolic processes, and the basolateral membrane potential is a diffusion potential with K+and C1- the most permeable ions. After depolarizing the basolateral membrane with high serosal potassium bathing solutions and eliminating the apical membrane as a rate limiting step for ion movement using the polyene antibiotic nystatin, we found that the addition of equal aliquots of NaCl to both solutions caused the basolateral membrane potential to hyperpolarize by up to 20mV (cell interior negative). This potential was reduced by 80% within 3 min of the addition of ouabain to the serosal solution. This hyperpolarization most probably represents a ouabain sensitive active transport process sensitive to intracellular Na+. An equivalent electrical circuit for Na+ transport across rabbit urinary bladder is derived, tested, and compared to previous results. This circuit is also used to predict the effects that microelectrode impalement damage will have on individual membrane potentials as well as time-dependent phenomena; e.g., effect of amiloride on apical and basolateral membrane potentials.


Nuclear magnetic resonance studies in liposomes: effects of steroids on lecithin fatty acyl chain mobility. The effects of fourteen sterols on the NMR spectra of liposomes derived from egg yolk phosphatidylcholines were studied by continuous-wave and Fourier-transform measurements at 60 MHz. Sterols were compared for their ability to broaden the acyl methylene resonances of phosphatidylcholine, when incorporated into liposomes at 25% molar ratio. The ratio of the phosphatidylcholine peake heights (acyl methylene: choline N-methyl) was used as a criterion of the relative condensing activity for the different sterols. This ratio was inversely proportional to the molar volume of the incorporated sterol, as measured by the parachor of the compound. Small sterols had little condensing effect, and the larger sterols such as cholesterol and ergosterol had maximum condensing effects. The study confirmed the importance of the sterol side-chain at C-17 as a requirement for sterol-phospholipid interaction.


Morphology of egg phosphatidylcholine-cholesterole single-bilayer vesicles, studied by freeze-etch electron microscopy. Homogeneous, small, single-bilayer vesicles were prepared from egg phosphatidylcholine with various concentrations of cholesterol by ultrasonic dispersion in 0.1 M KCl, 0.01 M Tris, pH 8.0, buffer, followed by gel chromatography. The shape and size distributions of the fractionated vesicles were investigated for preparations with cholesterol compositions from 0 to 50 moles/100 moles, using freeze-etch electron microscopy. The size distribution was estimated from the shadow width of vesicles which were exposed by etching and the vesicle shape was checked by comparing the images obtained by tilting the replicas. The widths of the vesicle diameter distributions were relatively broad, corresponding to standard deviations in the range 60--90 A, but showing no systematic variation with cholesterol composition. In all cases it was found that 70% of the vesicle diameters lay within 150 A of the modal value. The apparent vesicle diameters remained constant for cholesterol compositions up to 20 moles/100 moles (modal diameter = 330 +/- 20 A, mean diameter = 350 +/- 3 A), but there was a sharp net increase in diameter at 30 moles cholesterol/100 moles reaching a model diameter of 430 +/- 20 A (mean diameter = 430 +/- 3 A) at 50 moles cholesterol/100 moles. Using the tilted microscope stage it was found that all vesicles were spherical at all cholesterol compositions studied, including those above 30 moles cholesterol/100 moles. The molecular mechanism by which cholesterol controls the vesicle size is discussed in terms of the asymmetric distribution of cholesterol across the vesicle bilayer.


Ion transport across the isolated intestinal mucosa of the winter flounder, Pseudopleuronectes americanus. I. Functional and structural properties of cellular and paracellular pathways for Na and Cl. The isolated intestinal mucosa of the flounder, Pseudopleuronectes americanus, when bathed in a 20 mM HCO3-Ringer's solution bubbled with 1% CO2 in O2, generated a serosa-negative PD and, when short-circuited, absorbed Cl at almost 3 times the rate of Na. Reducing HCO3 to 5 mM decreased the net Cl flux by more than 60%. The following results suggest that, despite the PD, Na and Cl transport processes are nonelectrically coupled: replacing all Na with choline abolished both the PD and net Cl flux; replacing all Cl with SO4 and mannitol abolished the PD and the net Na flux; and adding ouabain (to 0.5 mM) abolished the PD and the net Cl flux. Nearly all of the unidirectional serosa-to-mucosa Cl flux (JClsm) seemed to be paracellular since it varied with PD and Cl concentration in a manner consistent with simple diffusion. JClsm was only about one-fourth of JNasm, suggesting that the paracellular pathway is highly cation-selective. The data can be explained by the following model: (i) Na and Cl uptake across the brush border are coupled 1 : 1; Na is pumped into the lateral space and Cl follows passively, elevating the salt concentration there; (ii) the tight junction is permeable to Na but relatively impermeable to Cl; and (iii) resistance to Na diffusion is greater in the lateral space (considered in its entirety) than in the tight junction. If these assumptions are correct, the serosa-negative transmural PD is due mainly to a salt diffusion potential across the tight junction and, under short-circuit condition, most of the Na pumped into the lateral space diffuses back into the luminal solution, whereas most of the Cl enters the serosal solution. Morphological features of the epithelium support this interpretation: the cells are unusually long (60 micrometer); there is little distension of the apical 12 micrometer of the lateral space during active fluid absorption; and distension distal to this region is intermittently constricted by desmosomes.


A thermodynamic analysis of the correlation between active Na+ transport and the rate of oxygen consumption in epithelia. Active transport in epithelia is discussed in terms of the relationships between oxygen consumption and sodium flux as affected by each of the two corresponding thermodynamic forces. Analysis is presented of the use of nonequilibrium thermodynamics as a total in elucidating coupling and stoichiometry, and in evaluating drug action in the system. The analysis leads to the quantitative characterization of active transport in "two-flow" systems in terms of two plots: oxygen consumption nad sodium flow, each as a function of electrical potential difference, at constant affinity and constant concentrations. The relevant characteristic parameters are then shown to be represented by the slopes and intercepts of the two plots, the ratios of the slopes and of the intercepts, and by  the difference--as well as the ratio--of the ratios. Distinction is made between experimental conditions in which the phenomenological coefficients remain constant and those in which these coefficients undergo appreciable changes. In terms of the above analysis, and examination is made of the effect of commonly used drugs. It is shown that while drugs may effect both the affinity and the phenomenological coefficients, they invariably affect the latter--at least in the cases hitherto reported.


Energy-dependence of phlorizin binding to isolated renal microvillus membranes. Evidence concerning the mechanism of coupling between the electrochemical Na+ gradient the sugar transport. In order to elucidate the mechanism by which the electrochemical Na+ gradient energizes glucose transport, the energy-dependence of high affinity phlorizin binding to isolated renal microvillus membrane vesicles was examined. Phlorizin is a competitive inhibitor of glucose transport but is not itself transported. Extravesicular Na+ accelerated the rate of phlorizin binding and inhibited the rate of dissociation of bound glycoside. Maneuvers to enhance intravesicular electronegativity stimulated phlorizin uptake and those to enhance intravesicular electronegativity stimulated phlorizin uptake and those to enhance intravesicular electropositivity inhibited. However, alterations in electrical potential were without effect on the rate release of bound phlorizin. Intravesicular Na+ inhibited the phlorizin uptake rate. The results are consistent with a model of the glucose transporter in which (i) Na+ increases the binding affinity of the carrier, (ii) the free carrier is negatively charged, and (iii) the translocation of the carrier is inhibited by the binding of Na+ in the absence of sugar. The electrochemical Na+ gradient thus energizes both glucose transport and phlorizin binding through its effect on the affinity and appearance of the free carrier at the membrane surface rather than through an effect on sugar translocation per se.


Imagery and verbal mediation in paired-associate learning of educable mentally retarded adolescents. PA learning was investigated among sixty educable mentally retarded adolescents as a function of variations in image-evoking potential of the response members and of instructions to utilise a verbal mediation strategy. The data indicated that performance with verbal mediation instruction surpassed that under non-mediation instruction conditions regardless of imagery level. Results were discussed in terms of Paivio's conceptual peg hypothesis as well as the EMR's deficiency in input organisation.


Hospital and community mortality rates among the retarded. The findings of McCurley et al. are generally replicated by this study. Community rates are usually lower than those of comparable institutional residents, except for convalescent hospitals used for the care of the profoundly retarded in the United States. Attention is drawn to the sharp mortality difference between ambulatory and non-ambulatory retarded individuals and the affect of the ability to walk can have on the estimation of mortality rates. The ambulation factor should be considered more routinely in future studies. Finally, a revision of the usual method of estimation of age at death was attempted. The utility of the method, similar to standardisation procedures widely used in demography, provides estimates which are more directly comparable between studies.


An analysis of verbal-performance intelligence quotient discrepancies in the Wechsler Adult Intelligence Scale results of mentally subnormal hospital patients. Verbal-Performance IQ discrepancies on the WAIS have been of much interest to clinical psychologists. They have been related, amongst other things, to different types of brain damage and in studies of the mentally subnormal, to successful adjustment to the outside world. This paper looks more closely at such discrepancies obtained by patients in a hospital for the mentally subnormal. These discrepancies are found to be both frequent related to Full Scale IQ. The pattern that emerges remains constant if scaled scores are considered or if the subtests are re-arranged according to Cohen's A and B factors. It is argued that these findings imply caution in the use of the discrepancy measure as a diagnostic or predictive indicator in this population.


Mental subnormality in Northern Ireland. A prevalence survey of mental subnormality in Northern Ireland was carried out on lines similar to an earlier investigation by MacKay (1971). In a general population of one and a half million there were 6,854 ascertained subnormal individuals. The male : female ratio was 1. 14 :1. Approximately one in three subnormal people was under residential care. The prevalence of severe subnormality (IQ less than 50) in the 15-19 year old group was 4.81. The findings do not support the "steady rate" theory of severe subnormality.


Jadassohn's naevus phakomatosis: I. A report of two cases. Two typical cases of Jadassohn's Naevus Phakomatosis are reported, with full clinical details, history and the results of investigations. Neurosurgery was necessary in one case so that the macroscopical appearance of the brain and histological findings of portions of the brain removed are described.


A correlative microscopical analysis of differentiating ovarian follicles of mammals. The mammalian ovary has been studied by optical microscopy and by scanning and transmission electron microscopy with the purpose of presenting an integrated view of the differentiating mammalian follicle. During follicular development, changes in the granulosa cells are particularly noteworthy and include dramatic modifications in cell shape coincident with antrum formation. The cytoplasmic processes of those granulosa cells immediately surrounding the oocyte, as well as the more peripheral granulosa cells comprising a second and third layer, traverse the zona pellucida, infrequently interdigitate with the microvilli of the egg, and make both desmosomal and gap junction contacts with the oocyte. The zona pellucida is thus distinguished by numerous fenestrations of varying diameters. The membrana limitans (basal lamina) is a bipartite structure composed of (a) a homogenous stratum upon which the peripheral layer of granulosa cells rests, and (b) an outer region of collagen-like fibers. The specific advantages and limitations of the different methodologies utilized to study folliculo-genesis are discussed.


Cyclic changes in fine structure of the epithelium lining the ovary of the viviparous teleost, Cymatogaster aggregata (Perciformes: Embiotocidae). The most striking morphological feature of the ovarian epithelium of Cymatogaster is the presence of intercellular dilations during much of the year. These dilations increase markedly in volume during the several months prior to ovulation and fertilization, and decrease in volume during the months of embryogenesis and gestation. The epithelium then returns to its initial, relatively undifferentiated state. The extracellular material within the dilations likely is synthesized in the cells adjacent to or within the dilations. Apparently most of this material is released into the ovarian lumen when the apicolateral margins of adjacent epithelial cells pull apart; possibly it serves as nutrient for developing embryos. In addition to supporting embryogenesis, the ovarian epithelium also apparently is involved in sperm storage. Sperm are maintained within pockets in the ovarian epithelium for the several months between insemination and fertilization. The cells lining the sperm pocket do not develop the intercellular dilations characteristic of most of the ovarian epithelium, and sperm remain associated only with the sperm pocket cells.


Further scanning electron microscope studies of lizard auditory papillae. The papillae basilares of 12 species of lizards from seven different families were studied by SEM. The iguanids, Sceloporus magister and S. occidentalis, have typical "iguanid type" papillae with central short-ciliated unidirectional hair cell segments and apical and basal long-ciliated bidirectional hair cell segments. These species of Sceloporus are unique among iquanids in that the bidirectional segments consist of but two rows of hair cells. The agamids, Agama agama and Calotes nigrolabius, have an "agamid-anguid type" papilla consisting of an apical short-ciliated unidirectional segment. Agama agama is unusual in having a few long-ciliated hair cells at the apical end of the apical short-ciliated segment. The agamid, Uromastix sp., has an "iguanid type" papilla with a central short-ciliated unidirectional segment and apical and basal bidirectional segments. The anguid, Ophisaurus ventralis, has an "iguanid" papillar pattern with the short-ciliated segment centrally located. All the short-ciliated hair cells of the above species are covered by a limbus-attached tectorial network or cap and the long-ciliated hair cells, only by loose tectorial strands. The lacertids, Lacerta viridis and L. galloti, have papillae divided into two separate segments. The shorter apical segment consists of opposingly oriented, widely separated short-ciliated cells covered by a heavy tectorial membrane. The apical portion of the longer basal segment consists of unidirectionally oriented hair cells, while the greater part of the segment has opposingly oriented hair cells. The xantusiids, Xantusia vigilis and X. henshawi, have papillae made up of separate small apical segments and elongated basal segments. The apical hair cells are largely, but not exclusively, unidirectional and are covered by a heavy tectorial cap. The basal strip is bidirectional and the hair cells are covered by sallets. The kinocilial heads are arrowhead-shaped. The papilla of the cordylid, Cordylus jonesii, is very similar to that of Xantusia except that the apical segment is not completely separated from the basal strip. The papilla of the Varanus bengalensis is divided into a shorter apical and a longer basal segment. The hair cells of the entire apical and the basal three quarters of the basal segment are opposingly oriented, not with reference to the midpapillary axis but randomly to either the neural or abneural direction. The apical quarter of the basal segment contains unidirectional, abneurally oriented hair cells. The entire papilla is covered by a dense tectorial membrane. The functional correlations of the above structural variables are discussed.


Structure and ultrastructure of the testis and sperm formation in goodeid teleosts. Testis structure in four species of goodeid teleosts is described. Testicular tubules terminate blindly at the testis periphery where spermatogonia are located. In goodeid teleosts, development of sperm takes place synchronously within cysts whose periphery is made up of a single layer of Sertoli cells. Upon completion of spermiogenesis, spermiation ensues wherein sperm are shed, as spermatozeugmata, into the testis efferent duct system. Subsequently, Sertoli cells, which comprised the cyst periphery, transform into efferent duct cells. Sertoli cells phagocytize residual bodies and are involved in the formation of spermatozeugmata. The structure of the goodeid spermatozeugmatum is quite different from that observed in the related poeciliids. It is concluded, in view of this and other considerations, that the goodeids and poeciliids have independently evolved solutions to the problems of internal fertilization and gestation.


Papillary projections at the lingual margin in the striped dolphin, Stenella coeruleoalba, with special reference to their development and regression. Papillary projections along the anterolateral margin of the tongue were observed in fetal and young stages of the striped dolphin, Stenella coeruleoalba. Papillary projections appear in the prenatal period and attain maximum development in the early postnatal period. They almost disappear by weaning. Vestigial eminences remain at the corresponding region, but they completely disappear in the adult. The papillary projections observed differ markedly from the lingual papillae of the general mammalian tongue as they are temporary, localized at the anterolateral margin and large in size. The projections were also present in young individuals of some other dolphins. No taste buds could be seen on the projections in any of the stages of all specimens observed. Such projections may have important mechanical functions during suckling in these mammals.


The morphology of the mucous gland and its responses to prolactin in the skin of the red-spotted newt. The mucous gland of the red-spotted newt, Notophthalamus viridescens viridescens, Rafinesque was examined by histochemical and ultrastructural techniques and its cytological responses to various hormonal conditions were studied. Its secretory epithelial cells produce and release in merocrine fashion a neutral, unsulphated mucosubstance. The secretory epithelium is bounded peripherally by a thin, but apparent non-functional, myoepithelium. The duct of this mucous gland consists of a single keratinized tubular cell that extends from the neck region of the gland to the surface of the epidermis. Mucous secretion is absent or greatly reduced on the skins of newts maintained under laboratory conditions for a few weeks but reappears after injection of ovine prolactin. Mucous glands in laboratory conditioned animals show a 4-fold increase in volume brought about by the engorgement of their epithelial cells with secretory granules. Ovine prolactin reduces the volume of the glands to unconditioned levels with a corresponding reduction in granular content, suggesting that prolactin functions in the release of the granules. This view is reinforced by the findings that autotransplantation of the pituitary gland prevents the conditioning effect and that glandular volume increases in autotransplanted animals given ergocornine. Granular accumulation begins also in hypophysectomized newts but ceases after a week, indicating the need for some hypophyseal factor in the synthesis as well as the release of the granules. Ovine prolactin restores mucous glands of hypophysectomized newts to the unconditioned state. Contrary to earlier findings, ovine prolactin induces a reduction in the volume of the mucous gland in thyroidectomized newts.


Amino acid-directed nucleic acid synthesis. A possible mechanism in the origin of life. The fact that proteins contain only alpha-amino acids and that protein structure is determined by 3' leads to 5' linked ribonucleotides is postulated to be the result of the copolymerization of these molecules in the prebiotic environment. Ribonucleotides therefore represent partial degradation products and proteins represent a side reaction developing from copolymerization. The basic structural unit of copolymerization is a nucleotide substituted with an amino acid at the 2' postion. Characteristics of modern amino and ribonucleic acid structure are all consistent with and necessary for this hypothesis. The characteristics and individual base assignemnts of the code also provide strong support for origin from the postulated copolymers. All characteristics of the code can be accounted for by this single hypothesis.


Codons and nearest-neighbor nucleotide pairs in mammalian messenger RNA. The codons in four mammalian messenger RNAs (rabbit beta hemoglobin, rat pre-proinsulin, rat pre-growth hormone and human chorionic somatomammotropin) show a predominance of C and G in third nucleotide positions. The C:U ratio is about 2 to 1, and the G:A ratio is about 4 to 1. The possibility is discussed that this disproportionally resulted from DNA replicative errors that favor C.G pairs over A.T pairs, as found in the E. coli mut T strain. "Nearest neighbor" base pairs ("doublets") in the protein-coding regions of phiX174 and in four mammalian mRNAs have been compared. Mammalian mRNA has a low content of CpG in comparison with expectations from its C and G content.


Construction of phylogenetic trees for proteins and nucleic acids: empirical evaluation of alternative matrix methods. The methods of Fitch and Margoliash and of Farris for the construction of phylogenetic trees were compared. A phenetic clustering technique--the UPGMA method--was also considered. The three methods were applied to difference matrices obtained from comparison of macromolecules by immunological, DNA hybridization, electrophoretic, and amino acid sequencing techniques. To evaluate the results, we used the goodness-of-fit criterion. In some instances, the F-M and Farris methods gave a comparably good fit of the output to the input data, though in most cases the F-M procedure gave a much better fit. By the fit criterion, the UPGMA procedure was on the average better than the Farris method but not as good as the F-M procedure. On the basis of the results given in this report and the goodness-of-fit criterion, it is suggested that where input data are likely to include overestimates as well as true estimates and underestimates of the actual distances between taxonomic units, the F-M method is the most reasonable to use for constructing phylogenies from distance matrices. Immunological, DNA hybridization, and electrophoretic data fall into this category. By contrast, where it is known that each input datum is indeed either a true estimate or an underestimate of the actual distance between 2 taxonomic units, the Farris procedure appears, on theoretical grounds, to be the matrix method of choice. Amino acid and nucleotide sequence data are in this category.


A method for detecting distant evolutionary relationships between protein or nucleic acid sequences in the presence of deletions or insertions. A method for detecting homology between two protein or nucleic acid sequences which require insertions or deletions for optimum alignment has been devised for use with a computer. Sequences are assessed for possible relationship by Monte Carlo methods involving comparisons between the alignment of the real sequences and alignments of randomly scrambled sequences of the same composition as the real sequences, each alignment having the optimum number of gaps. As each gap is successively introduced into a comparison (real or random) a maximum score is determined from the similarity of the aligned residues. From the distribution of the maximum alignment scores of randomly scrambled sequences having the same number of gaps, the percentage of random comparisons having higher scores is determined, and the smallest of these percentage levels for each pair of sequences (real or random) indicates the optimum alignment. The fraction of the comparisons of random sequences having percentage levels at their optimum alignment below that of the real sequence comparison at its optimum estimates the probability that such an alignment might have arisen by chance. Related sequences are detected since their optimum alignment score, by virtue of a contribution from ancestral homology in addition to optimised random considerations, occupies a more extreme position in the appropriate frequency distribution of score than do the majority of optimum scores of randomly scrambled sequences in their appropriate distributions. Application of this 'optimum match' method of sequence comparison shows that the sensitivity of the 'maximum match' method of Needleman and Wunsch (1970) decreases quite dramatically with sequence comparisons which require only a few gaps for a reasonable alignment, or when sequences differ greatly in length. The 'maximum match' method as applied by Barker and Dayhoff (1972) has the additional disadvantage that deletions which have occurred in the longer of two homologous protein sequences further decrease the sensitivity of detection of relationship. The 'constrained match' method of Sankoff and Cedergren (1973) is seen to be misleading since large increments in the alignment score from added gaps do not necessarily result in a high total alignment score required to demonstrate sequence homology.


Bioorganic chemistry and the origin of life. A challenging theme in bioorganic chemistry is the unification of established theories of biochemistry and organic chemistry to provide new patterns for interpretation and experimentation. Especially relevant examples of such interactions can be drawn from the field of enzyme catalysis and, in particular, the role of cofactors therein. Knowledge of the chemical mechanisms by which some of the cofactors function has progressed rapidly with the aid of studies of the cofactors themselves (or compounds of related structure, "models") stripped of the accompanying apoenzyme. The striking successes in this field likely arise from a fundamental resemblance between bioorganic chemistry (especially coenzyme models) and chemical evolution before the appearance of coded polypeptide enzymes.


Formation of the imidazolides of dinucleotides under potentially prebiotic conditions. Imidazolides of dinucleotides such as ImpApA can be formed from the corresponding dinucleotides in a two-stage process, which gives up to 15% yields under potentially prebiotic conditions. First a solution of the dinucleotide and sodium trimetaphosphate is dried out at constant temperature and humidity. This produces polyphosphates such pnApA in excellent yield (greater than or equal to 80%). The products are dissolved in water, imidazole is added, and the solution is dried out again. This yields the 5'--phosphorimidazolides.


Radiolysis, racemization and the origin of molecular asymmetry in the biosphere. An investigation has been undertaken to determine whether ionizing radiation might engender racemization of optically active amino acids, along with their usual radiolysis. As prototypes, crystalline D- and L-leucine, as well as aqueous solutions of their sodium salts were exposed to the radiation from a 3000 Ci 60Co gamma-ray source. Gamma-ray doses which caused about 68% radiolysis of solid leucine left a residue which was about 5% racemized, while racemization proved even greater at lower doses for the dissolved sodium salts. In aqueous solution both percent degradation and percent racemization of the sodium salts were proportional to gamma-ray dosage within the range employed (1--27 x 10(6) rads). Implications of these observations for the origin of molecular asymmetry by the beta-decay parity violation mechanism are discussed.


Management of extremity with combined neurovascular and musculoskeletal trauma. Twenty-five civilians with combined neurovascular and musculo-skeletal trauma to 27 extremities were studied retrospectively. The mechanism of injury was crushing in 16, avulstion in six, and penetrating in three. Autogenous saphenous vein was used to restore arterial circulation in the majority. Nine patients had concurrent repair of venous injuries. Fractures were immobilized by a variety of techniques, the Hoffman external skeletal fixation being preferred. Immediate fasciotomy was performed in five patients and delayed fasciotomy in four. All patients had soft-tissue debridement and initial wound closure with split-skin grafts as biologic dressings. Three immediate amputations were the result of irreversible neurovascular and soft-tissue trauma. Sepsis played a role in three late amputations; delayed primary treatment,, irreversible neurologic injuries and extensive soft-tissue damage contributed. A carefully individualized multidisciplinary approach resulted in salvage of 20 of 27 severely injured extremities.


Shotgun injuries of the upper extremity. Although most reports of civilian gunshot injuries consist mainly of wounds inflicted by handguns, shotgun wounds deserve special consideration. Longrange shotgun wounds rarely pose a problem; however, medium- and close range wounds of the penetrating and perforating type may inflict substantial soft-tissue loss, bone defects and comminution, and loss of nerve and vessel continuity. Because of the complex and multiple system involvement by shotgun wounds, a greater challenge exists to obtain a successful, functional result. The challenge is most appropriately met by an aggressive approach of early operative exploration and debridement of the wound, internal stablization of the bony fragments, vascular repair when indicated, and exploration and identification of nerve deficits, followed by an early wound closure.


The significance of chest wall injury in the diagnosis of traumatic aneurysms of the thoracic aorta. It has been suggested that patients sustaining blunt chest injury severe enough to result insignificant bony injury to the thorax may have traumatic aneurysms of the thoracic aorta in the absence of th widened mediastinum on plain film. To test the validity of this hypothesis, we performed aortograms on 14 patients with severe blunt chest injury but an otherwise normal chese X-ray. None of these patients was found to have an aortic injury. By contrast, of 21 patients with severe chest injury and a widened mediastinum who underwent thoracic aortography eight were found to have traumatic aneurysms of the thoracic aorta. These results suggest that in the absence of a widened mediastinum, severe chest wall injury is not an indication for aortography.


Management of fractures of the supraorbital rim. The frequency of supraorbital rim fractures is increasing as incidence of motorcycle and bicycle accidents increases. These fractures are frequently depressed, comminuted, and often extend into the frontal sinus. Open reduction and fixation are the treatment of choice. Adequate debridement and cleansing with preservation of periosteum and blood supply are recommended. Unstable fragments can be fixed to the frontal bone or stabilized by suturing the torn periosteum. Severely comminuted supraorbital frontal sinus fractures may require stabilization via frontal sinus pack or balloon. We feel the latter is preferable and both Foley and Fogarty catheters have been successfully used.


Analysis of treatment problems in subtraochanteric fractures of the femur. In a retrospective study of 82 subtrochanteric fractures of the femur in the St. Paul-Ramsey Hospital, there were 32 treated by traction, 50 by open reduction and internal fixation. In adults 50% of those treated by traction had undesirable results using strict criteria for varus, shortening, and rotational deformity: 21% of those treated by operation had undesirable results due to varus, rotational deformity, medial migration of the distal fragment, and nonunion. Good resutls are related to stable reduction and individualization of a particular implant based on the fracture pattern, including reconstruction of the medial cortical wall, and close contact of the fracture fragments during healing. If reduction is not achievable, bone grafting and extra protection are required. If reduction can be predicted as not achievable, good results can be obtained with traction although the healing period is longer. In the presence of a residual gap in the medial surface of the femur in the region of the lesser trochanter, poor results are frequent.


Regional burn survey: two years of hospitalized burned patients in central New York. A 2-year survey of burn victims in a  15-county region was conducted to help define the need for a burn unit. There were 1,165 patients hospitalized for burn care; 58 patients were transferred; 32 to more sophisticated facilities, 15 out of state. The mean hospitalization rate was 33/100,000; 95/100,000 for persons under 2 year old. The 42 hospitals, in the region treated an average of 14 burn patients each year. Scalds accounted for 39% of all burns and 85% of burns in children under 2. Burn-related deaths numbered 143: 4/100,000. House fires were responsible for 90 deaths. Despite incomplete records and the lack of firm criteria for burn severity, regional burn data describe the health care system, as it relates to burns, and identify high risk groups. The range inseverity of thermal injuries is great; the quality of care provided is difficult to assess.


Cervical fractures and fracture-dislocations sustained without head impact. Because of its flexibility and structure, the cervical spine is disposed to various mechanisms of injury: although not so common as injuries caused by head impacts, cervical fractures and/or fracture-dislocations have been reported without direct impact to the head. Some cervical injuries reported have been sustained by wearers of lap and shoulder belts in auto accidents; however, we do not consider belt use a potential hazard because ample evidence has accrued in the medical and engineering literature to document general injury and fatality reduction by use of seatbelts. We believe that in many instances occupants would be more seriously injured or killed were belts not worn. The present paper reviews reports of cervical injuries without head impact found in the literature and case histories of such injuries from the Highway Safety Research Institute of The University of Michigan, as well as experimental studies in animals, cadavers, and volunteer subjects.


Traumatic thoracobiliary (pleurobiliary and bronchobiliary) fistulas: clinical and review study. Thoracobiliary fistulas are rare complications of thoracoabdominal trauma, with high morbidity and potentially high mortality. Our experience with four cases and 12 other cases collected from the literature are reviewed. All patients were male and average age was 25 years. Five had blunt trauma, three had stab wounds, and eight, gunshot wounds. All had diaphragmatic and hepatic injuries. Bronchobiliary fistulas with biliptysis developed in seven patients. Fever, cough, chest and RUQ pains were the most common presenting symptoms. Pleural effusion and elevated right hemidiaphragm were the most common X-ray findings. Bile empyema developed in 2/3 of the patients. Early diagnosis, tube thoracostomy with adequate drainage of all subphrenic billious collections, and secure closure of all diaphragmatic perforations are essential in successful management of most of these fistulas. Thoracotomy, however, is indicated in chronic and complicated fistulas, and should not be delayed beyond 3 weeks. Judicious use of appropriate antibiotics is a necessary adjunct to adequate surgical management of these fistulas. All 16 patients survived.


Survival following a gunshot wound of the abdominal aorta and inferior vena cava. A case with survival following a point-blank .32 caliber gunshot wound of the abdominal aorta and inferior vena cava is presented. The patient, a young male also had multiple other abdominal injuries. A Dacron graft was used in the aorta, lateral suture in the vena cava, other injuries were repaired, and antibiotic treatment and irrigation performed. Packed red blood cells, Ringer's lactate, Plasmanate and nutritional support with medium chain triglycerides and ketones by mouth and amino acids by IV were given.


Sequence complexity and relative abundance of vaccinia virus mRNA's synthesized in vivo and in vitro. The sequence complexity and relative abundance of vaccinia virus mRNA's, synthesized in vivo and in vitro, have been measured by DNA-RNA hybridization. Up to 42% of [3H]thymidine-labeled virus DNA can be protected from digestion with nuclease S1, a single-strand specific nuclease, after annealing to excess polyadenylylated mRNA obtained at 7 h after infection. In contrast, only 26% of vaccinia virus DNA is protected when hybridized to polyadenylylated RNA obtained at 2 h after infection in the presence of an inhibitor of DNA synthesis. That the 94 kilobases transcribed early are a subset of the 152 kilobases present late was suggested by hybridization of DNA with a mixture of early and late RNAs. Some control of transcription is lost when virus purified by procedures that include sonic treatment is used for infection since under these conditions similar proportions of DNA are protected by either excess early or late RNA. Excess RNA, synthesized in vitro by enzymes within purified vaccinia virus particles, hybridized to approximately the same fraction of the DNA as did RNA present at late times in vivo. A second type of transcriptional control was demonstrated by kinetic analysis of the hybridization of polyadenylylated RNA to labeled DNA. With virion DNA used as the probe, a single abundance class for early RNA, two classes differing 11-fold in abundance for late RNA, and two classes differing 43-fold in abundance for in vitro RNA were found. To be able to detect high-abundance RNAs of very low sequence complexity, labeled complementary DNA probes to early, late, and in vitro polyadenylylated RNA  were used. Evidence that, at late times, RNAs totaling 9 kilobases of sequence complexity are present 40 to 500 times more frequently than the bulk of the virus-specific RNA was obtained. In contrast, the highest abundance class of RNA present at 2 h after infection corresponded to 7 kilobases present in only a 13-fold molar excess over the majority of virus-specific sequences. RNA synthesized in vitro was found to contain a small amount of sequence information, approximately 2 kilobases, which occurred 150 times more frequently than the majority of viral sequences. Studies using hybridization of viral DNA to labeled complementary DNA probes also suggested that 52 to 59% of the polyadenylylated RNA present at 2 h after infection and 82 to 92% of that at 7 h are virus specific.


Heat inactivation of vaccinia virus particle-associated functions: properties of heated particles in vivo and in vitro. The heat inactivation characteristics of several vaccinia virus particle-associated functions known to be involved in the transcription of the genome were examined. All functions were more resistant to heat than infectivity. Noninfectious particles were generated which exhibited significant levels of activity of all enzymes examined, and their properties were investigaed both in vitro and in vivo. RNA was synthesized in vitro by such particles, although transport of the RNA into the surrounding medium was defective. This RNA was larger than that made in normal particles but it was polyadenylated and functioned in vitro as a message coding for normal early proteins. The sequences transcribed were similar to those transcribed in normal particles, and we suggest that the production of abnormally large RNA is due to a defect in transcriptional termination. We could not detect any virus-specific protein or RNA synthesis in cells exposed to these inactivated particles and conclude that the loss of infectivity caused by heating is due to a general decline in the activities of a number of particle functions.