Retroperitoneal fibrosis simulating carcinoma of the cervix.

Retroperitoneal fibrosis generally occurs above the pelvic brim and is rarely encountered by the gynecologist. In the case presented, the fibrosis first became manifest in the pelvis and simulated metastatic carcinoma of the cervix. Treatment with cyclophosphamide and prednisone produced an apparent remission.


Childhood lichen sclerosus.

Presented is a case of a 6-year-old girl with biopsy-proved lichen sclerosus et atrophicus (LSA) localized to the anogenital region. She was seen approximately 3 months after the development of vulvar pruritus and burning on micturition. Following vulvar biopsies the patient was treated with hydrocortisone cream. Four months postbiopsy the patient is asymptomatic but with the coalesced white plaques remaining. Although cases benefiting from such various regimens as estrogen creams have been reported in the literature, the major benefit of therapy is relief of symptoms. This may be more safely accomplished with treatment of any vaginal discharge and the use of topical hydrocortisone cream. In children with regression of lichen sclerosus, complete resolution is common. No definite relationship to the menarche is documented.


Diffuse leiomyomatosis of the uterus precluding myomectomy.

Two cases of symmetrical uterine enlargement, with widespread involvement of the myometrium by innumerable leiomyomata, mainly of small and microscopic size, are reported. This unusual leiomyomatous enlargement of the uterus precludes myomectomy. A review of the literature revealed only 3 previous cases of this condition. The designation of diffuse leiomyomatosis of the uterus is proposed. The pathogenesis and differential diagnosis are discussed.


Primary pure insular ovarian carcinoids.

Ovarian carcinoids are generally found in association with teratomatous elements. Reported are the 23rd and 24th primary pure insular ovarian carcinoids. One of the cases presented initially with carcinoid heart disease.


Chylous metrorrhea.

Chylous is an extremely unusual cause of leukorrhea. The diagnosis is established by verification of the chylous nature of the discharge, documentation of its uterine origin, and lymphangiographic demonstration of dilated pelvic lymphatics with uterine reflux. Surgical excision of the incompetent lymphatic channels is the treatment of choice.


Adenocarcinoma of the vagina in a patient with gonadal dysgenesis.

Adenocarcinoma of the vagina is an uncommon tumor. Many theories have been postulated for its etiology and tissue origin. Its occurrence in young women exposed in utero to diethylstilbestrol has pointed to estrogen influence as a possible etiologic factor. A case of adenocarcinoma of the vagina in a patient with gonadal dysgenesis is presented, and histologic and electron-microscopic observations are discussed. This patient is unique in that development of the vaginal neoplasm occurred in the absence of estrogen influence.


Premature ovarian failure and hypothyroidism associated with sicca syndrome.

Two cases of premature ovarian failure, hypothyroidism, and sicca syndrome are described. To our knowledge, this association of sicca syndrome and multiglandular deficiency has not been previously reported. The finding of specific organ antibodies, as well as antibodies to nonorgan antigens in the 2 cases studied, supports the hypothesis that these rare clinical conditions may share a common autoimmune pathogenesis.


The effect of phacoemulsification on the corneal endothelium.

Endothelial cell densities were measured following intracapsular cataract extraction and phacoemulsification in the same patients. Phacoemulsification caused 29 percent more endothelial cell loss than intracapsular cataract extraction (p less than .001). The degree of endothelial damage with phacoemulsification appeared to be age related and was minimal in the younger patients.


Vitrectomy instrumentation for surgical evacuation of total anterior chamber hyphema and control of recurrent anterior chamber hemorrhage.

A patient with recurrent bleeding during hyphema extraction with the O'Malley ocutome was treated by elevation of the intraocular pressure to 50 mm Hg for 5 minutes with fluid from the infusing needle. When intraocular pressure was returned to normal, there was cessation of bleeding and postoperatively the anterior chamber remained free of blood. Elevation of intraocular pressure is offered as an initial alternative to air injection or cyclodiathermy for control of bleeding during hyphema extraction.


Calculation of the change in corneal astigmatism following cataract extraction.

Obtaining a minimal amount of postoperative astigmatism following cataract surgery is becoming increasingly important. One aspect of the patient's surgery which should not be overlooked is the preoperative keratometry which provides a basis for preoperative planning of surgical technique to be used and a point of reference for determining the amount of change in astigmatism produced by the surgery. Analysis of the surgically induced change in astigmatism using the calculations described in this paper will allow the surgeon to evaluate his own techniques and to maximize his potential for obtaining consistently good postoperative astigmatic results without the need for suture removal. The method presented is based upon concepts in common use in surgical ophthalmology and requires only simple mathematical procedures, familiar to all with a background in algebra and trigonometry.


A first year's experience with intraocular lens implantation.

A microsurgical modification of Binkhorst's "open sky" technique of extracapsular cataract extraction was developed for intraocular lens implantation. Clear visualization of both anterior and posterior capsule is stressed and risky aspiration is minimized. Thirteen cases operated upon in the first year are described. Synechiae to the haptics occurred when mydriasis was not prompt. All but one obtained useful naked acuity. Binocularity depended chiefly upon the acuity of the opposite eye. Pre-calculation of lens power reduced the spread of postoperative refractive errors although deviation was greater than expected and myopia overaccentuated. High astigmatic errors occurred in three patients.


Trabeculectomy and modifications of trabeculectomy.

Seventy-four trabeculectomies have been reviewed and discussed. Intraocular pressure 20 mm Hg or lower was achieved in 74.2% at the end of six months and in 66% one year postoperatively. The influence of age and sex on postoperative maintainance of intraocular pressure has also been discussed. There was not a statistical difference in results when the sex of the patients were compared. Patients under age forty did poorly in this series as compared to patients over age forty-one. Tenonectomy and cautery to the posterior edges of the scleral flap have been beneficial. The insertion of a gel film or silastic implant under the posterior edge of the scleral flap has been studied but in too few patients to draw any valid conclusions. In general, our results have been satisfactory with very few operative or postoperative complications.


Diagnosis and management of anterior uveal tumors.

Iris fluorescein angiography is another useful method in the evaluation of anterior uveal tumors. Three cases are presented which indicate that, in the diagnosis and management of anterior uveal tumors, certain fluorescein angiographic patterns may suggest malignancy. The presence of early hyperfluorescence, additional tumor foci, interruption of the normal iris radial vascular pattern by dilated tortuous vessels, and late leakage of fluorescein are suspicious findings, and indicate the necessity for comprehensive evaluation of such tumors.


Central retinal artery occlusion after facial trauma.

A case of traumatic retrobulbar hemorrhage resulting in occlusion of the central retinal artery which was relieved by surgical drainage of the hematoma pocket is presented. Osmotic agents are of little value in such situations, and we suggest that, after trauma causing the clinical picture of a tense retrobulbar hemorrhage and central artery occlusion, the more vigorous approach to the patient is justified.


Prevention of postoperative vertical imbalance and ptosis.

A technique is described which has reduced our incidence of vertical muscle imbalance and ptosis following intraocular surgery. The eye is well fixated, bleeding is minimized, and the operative field is better exposed. It is a simple modification of the usual technique of globe fixation and should be considered by ocular surgeons to reduce the complications of iatrogenic muscle imbalance and ptosis.


Automated phakotomy and aspiration of soft congenital and traumatic cataracts.

The design and operation of an automated instrument for removal of a soft cataract through a small corneal incision has been described in a small series of young patients. The distinct advantages of the instrument and technique are the small single-entry corneal incision, the minimal manipulation on the part of the surgeon, the relative constancy of both the anatomical shape of the globe and of a predetermined intraocular pressure during the procedure, a decreased inflammatory response, and a rapid wound healing.


Total cataract extraction through a 3-mm incision: a report of 650 cases.

We treated 650 consecutive cases of phacoemulsification with total capsulectomy. More than 91% of cases had best corrected visual acuities of 20/40 or better. In those with vision of 20/100 or less (3.5%) no cause for decreased acuity could be related to the surgery; 94% of cases had less than 1.5 diopters of residual astigmatism. Vitreous loss, occurring in 2.9% of cases, could be related to initial inexperience and errors in technique rather than patient age. Postoperative complications included transient striate keratitis (2.3%), persistent corneal edema (one case), cystoid macular edema (2.8%), and aphakic retinal detachments (2.6%). There were no hyphemas, flat or shallow anterior chambers, or filtering blebs postoperatively. We believe that this technique of total cataract extraction through a 3-mm incision yields the same results as an intracapsular extraction, but with less complications, and all the benefits of a small limbal incision.


Intraocular lens weight and the vitreous.

Intraocular lenses, or their components of various weights and designs, were placed on and within the viterous of fresh human autopsy eyes. All devices were supported on the surface of the intact viterous and within the formed vitreous. All sank promptly through the disorganized vitreous. Advice against anterior vitrectomies at the time of implant surgery is offered.


A modified cyclodialysis spatula.

A cyclodialysis spatula specifically designed for glaucoma surgery is presented which facilitates the performance of the cyclodialysis procedure alone or in combination with cataract extraction and decreases the chance of inadvertent damage to the eye.


Illness behavior and depression compared in pain center and private practice patients.

Recent descriptions of illness behavior and personality factors in chronic pain patients reflect patient populations at clinics dealing with refractory, multiple referral pain problems. Pain patients from the University of Washington Pain Center were compared with patients from a private practice clinic with regard to illness behavior and depression. Private practice patients were significantly less depressed, showed less conviction of disease, general hypochondriasis, affect disturbance and were less somatically focussed than the Pain Center patients. Physicians in general practice treating pain patients should avoid forming stereotypes of chronic pain patients based on the experiences of referral clinics, for such characterizations may lead them to weigh psychologic factors too heavily in diagnosis.


Memory for pain.

Memory for head pain was assessed by means of the McGill Pain Questionnaire (MPQ). Sixteen neurosurgical patients were divided into two groups in order to examine the decay of memory over time; one group recalled pain after 5 days and the other recalled pain after one day and then again, after 5 days. Contrary to expectations, the recall of pain was surprisingly accurate. The memory for pain showed littled decay over time. The small subgroup of patients who made specific errors when recalling their pain comprised women who had high levels of pain and affect at the initial assessment. Overall, the findings provide some welcome reassurance about the accuracy and reliability of pain reports from memory.


Fine structure of sensory nerves in the rat cornea: an experimental nerve degeneration study.

Fine structure of nerve fibres and terminals in the rat cornea was studied after fixation with glutaraldehyde and osmium tetroxide or with potassium permanganate. Superior cervical and/or ciliary ganglionectomy as well as ophthalmic neurotomy were performed in order to verify the origin of the corneal nerves. In the control corneas axon profiles with granular vesicles were observed in the stroma. Other axons containing agranular vesicles were found both in the stroma and in the epithelium. Superior cervical ganglionectomy abolished only the axons containing granular vesicles but did not affect the corneal blink reflex. Ciliary ganglionectomy induced more conspicuous changes in both stromal and intraepithelial axon profiles. The corneal reflex was, however, normal. Some of the axons containing agranular vesicles also showed degenerative changes. However, intact axon profiles with agranular vesicles were seen even after extirpation of both the ciliary ganglion and the superior cervical ganglion (combined autonomic ganglionectomy). On the other hand, all axon profiles with agranular vesicles disappeared after coagulation of the ophthalmic and maxillary nerves (sensory denervation). This operation destroyed most of the axons in all parts of the cornea and abolished the blink reflex. It is concluded that the axon profiles in the corneal epithelium, containing agranular vesicles, are sensory axons of the trigeminal nerve. A possible role of the vesicles in sensory nerves is discussed.


Acupuncture analgesia in rabbits.

The aim of this study was to verify the validity and reliability of analgesia elicited by acupuncture stimulation in rabbits. Ninety-five experiments were performed using 21 adult animals. The reaction time of the avoidance response elicited by noxious heat stimulation on the snout, and the presence or absence of the start response elicited by pin-prick and clamping of the skin were studied. Bilateral electric acupuncture stimulation in the area of Tsu-san-li and Shang-chu-hsu points in the hind legs was used. The animals were either held in a soft bag, loosely attached by cords, or suspended in a hammock; the eyes were either free of blindfolded. On the basis of operational behavioral measurements, it was found that acupuncture stimulation did not produce analgesia in undisturbed, placid animals. However, during agitated or fighting periods and the immobility reflex-like state, sometimes associated with acupuncture maneuvers, long reaction times were observed. Pin-pricking and clamping stimulation of the skin were not reliable methods of noxious stimulation in the rabbit.


The needle effect in the relief of myofascial pain.

In reviewing techniques for therapeutic local anaesthesia of pain spots, it appeared that the common denominator was puncture by the needle and not the anaesthetic employed. The present study examines short- and long-term effects of dry needling in the treatment of chronic myofascial pain. 241 patients and 312 pain sites were treated by needling. When the most painful spot was touched by the needle, immediate analgesia without hypesthesia was observed in 86.8% of cases. Permanent relief of tenderness in the needled structure was obtained for 92 structures; relief for several months in 58; for several weeks in 63; and for several days in 32 out of 288 pain sites followed up. The effectiveness of treatment was related to the intensity of pain produced at the trigger zone, and to the precision with which the site of maximal tenderness was located by the needle. The immediate analgesia produced by needling the pain spot has been called the "needle effect".


Signal detection theory pain measures: empirical validation studies and adaptation-level effects.

Proponents of the use of signal detection theory (SDT) in the assessment of pain modulation have generally looked for changes in d' to indicate a reduction of sensory function, and a change in criterion to indicate a modification of the subject's response bias or attitudinal predisposition. In the first experiment, both assumptions failed to receive empirical verification. Discrimination d' was eqivalent before and after two strong levels of electrical current was reduced. The criterion parameter appeared to shift in a more conservative direction after the stimulus diminution. These results are used to question the validity of both detection and discrimination indices in the measurement of pain. An alternative means for describing the experimental results revealed a striking adaptation-level effect with implications for the assessment of both experimentally induced and endogenous pain. The outcome of a second experiment reinforced the adaptation-level theory interpretation of the results and provided additional evidence concerning the difficultuies in evaluating SDT parameters in studies of potential analgesics.


Grooming behaviour of domestic cattle.

Grooming behaviour patterns of domestic cattle on pasture were studied by observation of a small herd of cross-bred cows, their single-suckling calves and a bull. The investigation was accomplished by means of description of directly observed patterns as well as description from SP8 cinematographic recordings. The observed grooming behaviour was classified in the following 8 patterns: Licking, scratching with hindhoof, scratching with horn, shaking, striking one part of the body against another part, rubbing, pawing, social grooming. It is assumed that one function of grooming behaviour may be a merely cleansing one. Another function may be related to the establishment and maintenance of the social structure in the herd.


[Fluorimetric determination of ampicillin in calf serum (author's transl)].

The serum concentrations of ampicillin was determined in calves after oral and parenteral administration. Ampicillin was analyzed by a fluorimetric method which was found simple and reliable. When ampicillin at a dose of 12 mg/kg was given in a milk replacer, the serum concentrations was too low to be effective even against all ampicillin sensitive bacteria. This method of treatment may be used only in the treatment of enteritis, as it is reported in the literature that high ampicillin concentrations occur in the intestinal content and the intestinal mucosa. After intramuscular injection of recommended doses (4-10 mg/kg), high serum concentrations was reached soon after the injection. The drug is, however, excreted rapidly and treatment should be repeated at shorter intervals than usually is recommended.


[Fasciola hepatica in Denmark. A survey on 15 years diagnostic examination on bovine faeces samples (author's transl)].

The results of routine diagnostic examinations of 10,540 bovine faeces samples for eggs of Fasciola hepatica during the period 1963-1977 are evaluated. 0n an average, 10.4% of the samples were positive. The frequency of positive samples was highest among samples from cows (14.4%) lowest among samples from calves (1.5%). Of samples from heifers 10.1% were found positive. Calculated on a monthly basis, the percentage of positive samples showed a clear seasonal variation, reaching a peak in the period December-March. During the period 1973-1977, the annual percentage of positive samples showed a rather pronounced declining tendency, indicating a decrease in the occurrence of bovine Fasciola hepatica infection in Denmark.


Arthrosis with special reference to the elbow joint of young rapidly growing dogs. II. Occurrence, clinical and radiographical findings.

Occurrence, clinical and radiographical findings in ununited medial coronoid process in the ulna and osteochondritis dissecans in the humeral condyle in dogs are presented. One hundred and twelve dogs were examined because of forelimb lameness. Lesions were mostly seen in young dogs of heavy breeds especially the Rottweiler. The ratio male: female was about 2:1. Most of the dogs had bilateral lesions. The lameness varied between grade 1 and 3, judged according to a scale ranging from 1 to 5. The affected limbs were somewhat rotated outwards from the elbow and down. Since the ununited coronoid process is almost impossible to detect on a plain radiograph, it is necessary to look for the presence of secondary developed osteophytes, indicative of an arthrosis. Diagnosis is based upon clinical and radiographical findings, the age and the breed of the dog taken into consideration. Osteochondritis dissecans in the humeral condyle is usually easily seen on the dorsopalmar radiograph.


[Repeated freezing of bull semen (author's transl)].

Repeated freeze-thaw cycles have been used as a mean to predict the viability and fertility of bull semen. In order to investigate the level of fertility of bull semen that has been frozen, thawed and refrozen again, two split sample field trials were performed. 25 bulls were used in the trial, and inseminations were performed by 30 technicians. The semen was diluted to 27 million spermatozoas per dose in a skimmilk-fructose extender, and filled in the french mini-straw. The straws were coded by use of a batch number system. The one half of the straws was fixed to the freezing rampes. After freezing and transfering of the rampes to liquid nitrogen, the rampes were placed in a water-bath at + 35 degree C in 7 seconds. Immediately after thawing the straws they were transferred to a refrigidaire room at + 5 degree C, dried, remounted on the rampes and frozen again in the ordinary way. The other half of the straws were frozen according to the normal routine. The semen from the two treatments were distributed in equal numbers to the technicians who were not informed of the trial. The motility after refreezing had decreased and the percentage of intravital eosin spermatozoas after refreezing increased by 23, as an average. Fertility results were estimated as 60 days non returns after 1st inseminations. Single frozen semen: 1488 1st ins. 493 ret. 66,86 N.r.-% Refrozen semen: 1511 1st ins. 500 ret. 65,30 N.R.-% The trials indicate that further investigation should be performed to see if semen might be frozen concentrated, rediluted after thawing and refrozen for distribution to the technicians.


Compilation of tRNA sequences.

This compilation presents in a small space the tRNA sequences so far published in order to enable rapid orientation and comparison. The numbering of tRNAPhe from yeast is used as has been done earlier (1) but following the rules proposed by the participants of the Cold Spring Harbor Meeting on tRNA 1978 (2) (Fig. 1). This numbering allows comparisons with the three dimensional structure of tRNAPhe, the only structure known from X-ray analysis. The secondary structure of tRNAs is indicated by specific underlining. In the primary structure a nucleoside followed by a nucleoside in brackets or a modification in brackets denotes that both types of nucleosides can occupy this position. Part of a sequence in brackets designates a piece of sequence not unambiguously analyzed. Rare nucleosides are named according to the IUPAC-IUB rules (for some more complicated rare nucleosides and their identification see Table 1); those with lengthy names are given with the prefix x and specified in the footnotes. Footnotes are numbered according to the coordinates of the corresponding nucleoside and are indicated in the sequence by an asterisk. The references are restricted to the citation of the latest publication in those cases where several papers deal with one sequence. For additional information the reader is referred either to the original literature or to other tRNA sequence compilations (3--7). Mutant tRNAs are dealt with in a separate compilation prepared by J. Celis (see below). The compilers would welcome any information by the readers regarding missing material or erroneous presentation. On the basis of this numbering system computer printed compilations of tRNA sequences in a linear form and in cloverleaf form are in preparation.


Site specific endonuclease from Fusobacterium nucleatum.

Four different isolates of Fusobacterium nucleatum (A,C,D and E) contain restriction endonucleases of differing specificity. Whilst many of the endonucleases are isochizomers of known enzymes, two novel activities are Fnu DII which recognizes and cleaves the sequence 5'-CGCT-3'/3'-GCGC-5' AND Fnu EI which recognizes and cleaves the sequence 5'-GATC-3'/3'-CTAG-5' irrespective of the extent of methylation of the adenine residues.


Low resolution models of self-assembled histone fibers from X-ray diffraction studies.

X-ray diffraction data from self-assembled histone fibers are presented for three systems: H4, H3-H4, and the four core histones H2A, H2B, H3 and H4. These data have been obtained under conditions of high ionic strength and high protein concentration which are thought to promote histone conformation similar to that found in intact chromatin. The low angle equatorial scattering (R less than .05 A-1) is analysed, and, with additional constraints imposed by electron microscopy data, four low resolution fibrillar models are derived. Two features common to all the possible models are a maximum outer diameter of approximately 60 A and a subfibril diameter of approximately 25 A. It is the interference of the protein subfibrils across a central region of low electron density - a 10 A "hole" - which gives rise to the characteristic diffraction peak at 36 A. Possible relationships of the models of the histone fibers to the structure of the histone component of chromatin are suggested.


The 3' noncoding region of beta-globin mRNA is not essential for in vitro translation.

Rabbit beta globin DNA sequence, excised from plasmid pbetaG1, directs in vitro synthesis of beta-globin in a transcription-translation cell-free system, even after specific elimination of the entire 3'-noncoding region. A DNA restriction fragment carrying this 3' noncoding region and hybridized to globin mRNA cannot arrest the cell-free translation of beta-globin mRNA.


Studies on the association of the high mobility group non-histone chromatin proteins with isolated nucleosomes.

Nucleosomes have been isolated from rabbit thymus by sucrose gradient centrifugation, and their high mobility group (HMG) protein content analysed by electrophoresis on polyacrylamide gels. The results suggest that proteins HMG 14 and HMG 17 are associated with the core particle of the nucleosome, and that there are two or more sub-populations of both HMG 1 and HMG 2 molecules. One sub-population appears to be fairly tightly bound to the nucleosome, while another is rapidly released from the chromatin by digestion with micrococcal nuclease. The latter fraction may participate in a higher order folding of the nucleosomes.


A restriction enzyme from Fusobacterium nucleatum 4H which recognizes GCNGC.

A site-specific restriction endonuclease Fnu4H I isolated from Fusobacterium nucleatum 4H recognizes the DNA nucleotide sequence 5'G C N G C-3'/3'-C G N C G-5' and cleaves as indicated by the arrows.


Cell specific antiserum to chromosome scaffold proteins.

Antiserum has been raised to a chromosomal protein fraction specific for Hela cells. The immunoactivity is located in the transcriptionally inactive regions of log phase chromatin. Digestion of metaphase chromosomes results in the purification of the immunoactivity in the scaffold region of the chromosomes. Extensive nuclease digestion of the scaffolds results in loss of activity. The data suggest that some of the proteins in the scaffold area are both tight binding and cell specific and may therefore play a sophisticated role in gene expression.


Analysis of the attachment of replicating DNA to a nuclear matrix in mammalian interphase nuclei.

The attachment of replicating DNA to a rapidly sedimenting nuclear structure was investigated by digestion with various nucleases. When DNA was gradually removed by DNase I, pulse label incorporated during either 1 min or during 1 hour in the presence of arabinosylcytosine, remained preferentially attached to the nuclear structure. Single strand specific digestion by nuclease S1 or staphylococcal nuclease at low concentrations caused a release of about 30% of the pulse label, without significantly affecting the attachment of randomly labelled DNA. The released material had a low sedimentation coefficient and contained most of the Okasaki fragments. The remaining pulse label was less accessible to further digestion by double strand specific nuclease activity than the bulk DNA. The results suggest that an attachment of the replication fork to the nuclear structure occurs at sites behind but close to the branch point.


Preparation of polydeoxynucleotides linked to a solid support by coupling CNBr-activated cellulose with 5'-NH2-terminated oligo and poly(pdT)'s.

Synthetically-prepared 5'-NH2-dT(pdT)n oligomers (66,n=4 or 7) were immobilized on cyanogen bromide activated cellulose. The influence of temperature, pH, and ionic strength on the rate of the coupling process was studied. The oligomer 5'-NH2-DT(pdT)8 could be elongated enzymatically to the polymers 5'-NH2-dT(pdT)n (n=20, 51 and 84), which could be immobilized on cellulose. The cellulose-NH-dT(pdT)84 polymer thus obtained could be assembled to a new solid-state polymer e.g. poly(dA)290 . poly(/3H/dT)200, poly(dT)85-cellulose which, in turn, was a very convenient substrate for assaying DNA-ligase.


Multiacetylated forms of H4 are found in a putative transcriptionally competent chromatin fraction from trout testis.

We have examined the distribution of acetylated histones derived from various trout testis chromatin fractions of different composition. Our results indicate that a chromatin fraction, preferentially solubilized by micrococcal nuclease, containing the bulk of the HMG proteins and similar to a fraction released from intact trout nuclei and previously shown to be enriched in transcribed DNA sequences also possesses high levels of multiacetylated species of H4. Histones 2A, 2B and 3 are also acetylated in this particular chromatin fraction. Monoacetylated species of the 4 inner nucleosomal histones appear to be characteristic of the nucleohistone portion of trout testis chromatin.


Quantitative estimation of the contribution of pyrrolcarboxamide groups of the antibiotic distamycin A into specificity of its binding to DNA AT pairs.

Interaction of DNA with the analogs of the antibiotic distamycin A having different numbers of pyrrolcarboxamide groups and labeled with dansyl was studied. The binding isoterms of the analogs to synthetic polydeoxyribonucleotides were obtained. Analysis of the experimental data leads to the following conclusions: (1) the free energy of binding of the analogs to poly(dA).poly(dT) depends linearly on the number of amide groups in the molecule of the analog whereas attachment of each pyrrolcarboxamide group produces changes of 2 kcal/mole in the free energy; (2) attachment of a pyrrolcarboxamide unit to the GC pair results in the free energy change of 0.95 kcal/mole; (3) the binding of analogs to poly(dA).poly(dT) is a cooperative process, presumbly, dependent on conformational changes induced by the binding of analogs to DNA.


Cytidine 5'-diphosphate reductase activity in phytohemagglutinin stimulated human lymphocytes.

The optimal conditions and the effect of deoxyribonucleoside triphosphates were determined for CDP reductase activity in PHA-stimulated lymphocytes. The enzymatic reaction showed an absolute requirement for ATP. In the absence of ATP, only dATP showed a minor stimulation of the reduction of CDP to dCDP. During transformation the CDP reductase activity reached a maximum at the same time as the four deoxyribonucleoside triphosphate pools, corresponding to mid S-phase at about 50 h after PHA addition. The DNA polymerase activity reached a maximum at 57 h.


Synthesis of low molecular weight RNA components A, C and D by polymerase II in alpha-amanitin-resistant hamster cells.

In an attempt to establish which RNA polymerase catalyzes the synthesis of the low molecular weight RNA components A, C and D, Ama 1 cells (mutant Chinese hamster cells) were used in experiments with addition of alpha-amanitin. Ama 1 cells contain an altered RNA polymerase II which is 800 times more resistant towards inhibition by alpha-amanitin than the wild type enzyme. Alpha-amanitin (up to 200 microgram/ml) added to these cells does not affect the synthesis of the low molecular weight RNAs A, C and D. These data together with our previous data showing that alpha-amanitin (0.5 - 5.0 microgram/ml) preferentially inhibits the synthesis of A, C and D in normal cells indicate that RNA polymerase II catalyzes the synthesis of the low molecular weight RNA components A, C and D.


Extracellular nucleases of Alteromonas espejiana BAL 31.IV. The single strand-specific deoxyriboendonuclease activity as a probe for regions of altered secondary structure in negatively and positively supercoiled closed circular DNA.

The dependence of the initial rate of introduction of the first single-chain scission (initial nicking rate) into covalently closed circular phage PM2 DNA by the single strand-specific nuclease from Alteromonas espejiana BAL 31 upon the superhelix density (sigma) of the DNA has been examined. The initial nicking rate decreases with decreasing numbers of negative superhelical turns (decreasing values of -sigma), which behavior is characteristic of other single strand-specific nucleases as reported earlier. In contrast to earlier work, the initial nicking rates of closed circular DNAs by the action of the Alteromonas nuclease have been shown to be readily measurable at values of -sigma as low as 0.02. However, even at the elevated concentrations of enzyme and extended digestion periods required to cause nicking at an appreciable rate at near-zero values of sigma, closed circular DNA containing very few superhelical turns (form IO DNA) is not cleaved at a detectable rate. When this DNA is rendered positively supercoiled by ethidium bromide (EtdBr), it is not affected by the nuclease until very high positive values of sigma are attained, at which low rates of cleavage can be detected at elevated enzyme concentrations. The effects of EtdBr on the enzyme activity have been tested and are entirely insufficient to allow the interpretation of zero nicking rates as the result of inhibition of the nuclease activity by the dye. Positively supercoiled DNA is concluded not to contain regions having significant single-stranded character until values of sigma are reached which are very much higher than the values of -sigma for which negatively supercoiled DNAs behave as if they contain unpaired or weakly paired bases.


The influence of chromatin structure on the distribution of DNA repair synthesis studied by nuclease digestion.

The influence of chromatin structure on the distribution of DNA repair synthesis was studied by enzymatic digestion of "repair labeled" nuclei of mouse mammary cells: "repair labeled" nuclei were isolated from pregnancy mammary tissue fragments, treated in vitro with methylmethanesulfonate (MMS) or methylnitrosourea (MNU), and pulse-labeled with 3H-thymidine in the presence of hydroxyurea in the culture medium. Micrococcal nuclease digestion of "repair labeled" nuclei indicates that at early hours after treatment with the alkylating agents 70-80% of the total repair synthesis is located in the linker portion of the nucleosome. However, 6-12 hours after treatment DNA repair synthesis is more evenly distributed throughout the core and linker portion of the nucleosome. "Repair labeled" mammary cell nuclei were also digested with DNase I under conditions selective for transcriptionally active chromatin. A two-fold higher level of repair synthesis was found in the transcriptionally active chromatin of "repair labeled" nuclei isolated from MMS or MNU treated mammary fragments, pulse-labeled at different times after treatment. The results indicate that structural constitution of the chromatin may influence the distribution of DNA repair synthesis both at the nucleosome level, and at higher levels of chromatin organization. This may be due to 1) nonrandom base alkylation in chromatin or 2) areas in chromatin with increased accessibility for the repair enzymes to the alkylated bases.


Photochemical properties of Yt base in aqueous solution.

Photoreactivity of Yt base [I] has been studied in aqueous solution [pH approximately 6] saturated with oxygen. Two photoproducts (II,III], resulting from irradiation at lambda = 253.7 nm and lambda greater than or equal to 290 nm, were isolated and their structures determined. The quantum yield for Yt base disappearance [zeta dis] is 0.002 [lambda = 313 nm]. It was shown that dye-sensitized photooxidation of Yt base in aqueous solution occurs according to a Type I mechanism, as well as with participation of singlet state oxygen. Quantum yields, fluorescence decay times and phosphorescence of Yt base have been also determined.


Precise location of DNase I cutting sites in the nucleosome core determined by high resolution gel electrophoresis.

The precise locations of the DNase I cutting sites in the nucleosome core have been determined by analysis of the DNA products of a DNase I digestion of 32P end-labelled mucleosome cores on a high resolution gel electrophoresis system. This system is capable of resolving fragments of mixed sequence DNA differing by one base into the region of 160 bases in length. The DNase I cutting sites in the core are found to be spaced at multiples of about 10.4 (i.e. clearly different from 10.0) bases along the DNA, but show significant variations about this value. In addition to the location of the sites, the stagger between individual sites on opposite strands has been determined and is found to be inconsistent with at least one proposed mechanism for nuclease cleavage of chromatin DNA. Finally, a calculated distribution of fragment lengths in a DNase I digest of nuclei has been determined from the data obtained from the nucleosome core and found to be in reasonable agreement with the observed distribution. The periodicity of 10.4 is discussed with respect to the number of base pairs per turn of chromatin DNA and the number of superhelical turns of DNA per nucleosome.


A comparative study of G+C-rich satellite components of sheep and goat DNA.

Restriction fragment patterns of G+C-rich satellites of sheep and goat DNA were compared. The 1,712 g/cm3 satellites of both species appear homologous, consisting of repeats 760 base pairs long and showing coincidence of position of primary+ EcoRI, BamHI and most BspRI restriction target sites. The EcoRI and BamHI endonucleases produce mostly monomers of the repeating unit, while oligomers prevail in the A1uI and Bg1II digests. Species-specific differences in the frequency, position and mode of distribution of secondary+ restriction target sites for EcoRI, Bg1II and A1uI were observed. Unlike the 1,712 g/cm3 satellites, the 1,723 g/cm3 component of sheep DNA and the 1,719 g/cm3 material from goat DNA appear species--specific, since no homologous material could ever be detected in the DNA of the other species.


A new method for 3'-labelling of polyribonucleotides by phosphorylation with RNA ligase and its application to the 3'-modification for joining reactions.

P1-Adenosine 5'-P2-o-nitrobenzyl pyrophosphate (nbzlppA) has been synthesized as a substrate for T4 RNA ligase catalyzed 3'-phosphorylation. Incubation of oligoribonucleotides and nbzlppA with RNA ligase yielded oligoribonucleotides having a 3'-o-(o-nitrobenzyl) phosphate. Photochemical removal of the o-nitrobenzyl group provided the free 3'-phosphate. Using [P2-32P] nbzlppA, 3'-termini of oligoribonucleotides could be labelled with 32P. This reaction was applied to modify the 3'-end of donor molecules in joining reaction with RNA ligase. A trinucleotide U-A-G was converted to U-A-Gpnbzl and phosphorylated with polynucleotide kinase. pU-A-Gpnbzl was then joined to an acceptor trinucleotide A-U-G to yield A-U-G-U-A-Gp.


Mammalian mitochondrial transfer RNAs: chromatographic properties, size and origin.

Incubation of isolated rat liver mitochondria with radioactive amino acids resulted in the charging of tRNAs for arginine, asparagine, leucine, lysine, methionine, proline and valine. The aminoacyl-tRNAs were shown to be distinct from their cytosolic counterparts by chromatography on RPC-5. By electrophoresis on urea polyacrylamide slab gels it was found that all these mitochondrial aminoacyl-tRNAs were about 70-76 nucleotides long. The unique mitochondrial asparaginyl- and prolyl-tRNAs, not previously identified in mammalian cells, were shown to hybridize to mtDNA. Mitochondrial leucyl-tRNA separated into 3 peaks on RPC-5 and the first species was shown to be different than a combination of the other two by molecular size and partial RNase T1 digestion patterns. Each was coded by a separate gene on mtDNA as shown by partial additivity of hybridization. Separate genes for mitochondrial tRNAMetm and tRNAMetf, separated by RPC-5 chromatography, were also demonstrated. These results bring to 21 the number of individual tRNAs coded by mammalian mtDNA.


Characterisation of bacterial clones containing DNA sequences derived from Xenopus laevis vitellogenin mRNA.

A 1700 nucleotide DNA sequence derived from Xenopus vitellogenin mRNA has been cloned in the bacterial plasmid pBR322. The identity of the cloned sequence was verified in two ways. Firstly, the plasmid DNA was shown to hybridise to an RNA of the correct size (6,700 nucleotides). This was shown by in situ hybridisation to electrophoretically separated RNA and also by the formation of "R-loops" with purified vitellogenin mRNA. Then, using a novel procedure in which plasmid DNA covalently bound to diazotised paper is used to select complementary mRNA sequences, the cloned sequence was shown to hybridise to an mRNA which directed the synthesis of vitellogenin when translated in a reticulocyte lysate cell-free system.


Evidences of two different sets of histone genes active during embryogenesis of the sea urchin Paracentrotus lividus.

Histone mRNAs at different stages of development were purified by hybridization with the cloned homologous histone genes. The electrophoretic patterns of oocytes, 2-4 blastomeres, 64 cells and morula histone mRNAs was found to be identical, whereas the electrophoretic pattern of mesenchyme blastula histone mRNA was markedly different. The cloned histone DNA of P.lividus was hybridized with the RNA of each stage. The Tm was 74 degrees C in all cases except for the mesenchyme histone mRNAs whose Tm was 59 degrees C, thus suggesting that at least two different clusters of histone genes are active in the course of the sea urchin development.


A correlation between nucleosome spacer region susceptibility to DNase I and histone acetylation.

Hepatoma tissue culture (HTC) cell nuclei were digested with either DNase I or micrococcal nuclease and the nucleohistone digestion products fractionated by gel electrophoresis or exclusion chromatography. Under appropriate conditions, gel electrophoresis demonstrates that for both nucleases, only cleavages within the nucleosome spacer regions and not within the nucleosome core lead to freely migrating nucleohistone particles. These particles consist of nucleosome cores, nucleosomes and nucleosome oligomers. Following DNase I digestion and fractionation by exclusion chromatography, analysis of the histones indicates a direct relationship between increased spacer region susceptibility to nuclease and increased nucleosomal histone acetylation. Evidently digestion sites outside the regions of DNA protected by core histones can reflect the degree of acetylation of core histones. Such a relationship is not found when micrococcal nuclease is used to digest the samples.


Purification of specific adenovirus 2 RNAs by preparative hybridization and selective thermal elution.

A method is described for the preparation isolation of highly purified adenovirus RNA species. Cytoplasmic RNAs from cells infected with adenovirus 2 were selected by hybridization to viral DNA fragments bound to nitrocellulose membranes. A series of washes at elevated temperatures (50-70 degrees) determined conditions at which the true hybrids were stable but non-specific RNA was removed. This temperature has been found to correlate with the base composition of the DNA fragment. After washing at this predetermined temperature, the specific RNA was eluted at 85 degrees. The purity of the eluted RNA was greater than 95% as determined by size, sequence specificity, and template activity in an in vitro protein synthesizing system. The method described should be generally useful for purification of specific RNAs.


Urea-induced binding of histone 1 to nucleosomes lacking linker DNA.

The binding of H1 (and H5) to nucleosome core particles was demonstrated by separating mononucleosomes according to their DNA size on acrylamide gels containing high molarity urea. The presence of urea causes a redistribution of H1 so that it associates with some particles of all linker lengths, including no linker. When the urea is removed the H1 remains associated with particles of all DNA sizes if the different size classes are not mixed with each other. Therefore, urea can effect the transfer of H1 from particles with linker to particles with no linker. When nucleosomes of uniform DNA fragment length, some containing and some lacking H1, are re-electrophoresed under native conditions, they migrate as two widely separated bands. The mobilities of these variants do not depend on linker length and are identical to the mobilities of native H1-containing and H1-lacking particles. When the same collection of particles is electrophoresed in the presence of high molarity urea they migrate with a uniform mobility. These results suggest that H1-containing nucleosomes are conformationally different from H1-lacking particles, but that this difference is eliminated when histone-histone interactions are disrupted by urea.


DNA-histone interaction in the vicinity of replication points.

Chromatin replication was studied in isolated nuclei from Concanavalin A activated lymphocytes. Digestion with micrococcal nuclease revealed that the resistant fraction of in vitro replicated DNA is associated with nucleosomes. Earlier experiments had shown that the nuclease resistant fraction of nascent DNA is composed of fragments which are shorter than the nuclease resistant fragments of bulk DNA. In this communication we demonstrate that the short fragments of nascent DNA are differently bound to nucleosome like structures compared to bulk DNA. At 0.5 M NaCl a fraction of pulse labeled labeled DNA is released from these structures and appears as free double stranded DNA of about 140 base pair length (5S DNA) while the 185 pair fragments of mature replicated DNA remain attached to nucleosomes under these conditions. The experiments may indicate that the interaction of a fraction of replicating DNA with histones differs from that of bulk DNA.


Comparison of rat liver and Walker 256 carcinosarcoma tRNAs.

The complete nucleotide sequences of both rat liver and Walker 256 mammary carcinosarcoma tRNAAsn reveal that they are identical except for the nucleotide present in the wobble position of the anticodon loop. The rat liver tRNAAsn contains the Q nucleoside, whereas the tumour tRNAAsn contains an unmodified guanosine. The tRNAs from both tissues also show significant quantitative differences in the chromatographic mobilities for isoaccepting species of tRNAAsp, tRNAAsn, tRNAHis and tRNATyr. In addition, chromatographic shifts upon cyanogen bromide treatment and analyses of the alkaline hydrolysates of these tRNAs demonstrate that those of tumour origin contain significantly less Q and Q nucleoside than their normal rat liver counterparts.


A new procedure for purifying histone pairs H2A + H2B and H3 + H4 from chromatin using hydroxylapatite.

A method to purify histone groups H2A+H2B and H3+H4 using dissociation with NaCl and hydroxylapatite chromatography is presented. The procedure is simple, involves mild solvents, and provides milligram quantities of histones of high purity. The histone pairs prepared by this method can regenerate chromatin-like characteristics when combined and reconstituted with DNA.


Ultraviolet light-induced crosslinking of mRNA to proteins.

Irradiation of intact or EDTA-dissociated L-cell polyribosomes with 254 nm UV light at doses of 1-2 x 10(5) ergs/mm2 extensively crosslinks mRNA to proteins. The crosslinked mRNA-protein complexes can be isolated on the basis of buoyant density in urea-containing CS2SO4 gradients that dissociate non-covalent complexes. Crosslinking of mRNA can also be assayed by phenolchloroform extraction. mRNA recovered from the crosslinked complexes by digestion with proteinase K has the same electrophoretic mobility in polyacrylamide gels as unirradiated mRNA. Therefore, irradiation does not either crosslink RNA molecules to RNA molecules or break phosphodiester bonds. With these methods it has been found that more than 70% of high molecular weight polydisperse mRNA, but only 25-40% of histone mRNA, can be crosslinked to protein. On the basis of buoyant density the histone mRNA-protein complex had a protein content of 26%, whereas the mean protein content of most non-histone mRNA-protein complexes was 65%. It is concluded that most mRNA in polyribosomes is in close contact with proteins, and that histone mRNA can be crosslinked to many fewer proteins that most other mRNAs.


Virogenic BrdU and BrdU-sensitive DNA sequences are disproportionately concentrated in the template-active chromatin of rat embryo cells.

In order to characterize the molecular mechanism responsible for the BrdU-mediated activation of endogenous retrovirus from normal rat embryo cells, the previously reported selective distribution of bromouracil in DNA was correlated with the corresponding organization of the nucleo-protein complex in regard to nucleosome structure and template - active and -inactive chromatin. Following micrococcal nuclease digestion of chromatin labeled with either [(3)H]thymidine or [(3)H]BrdU, the amount and specific activities of the respective nucleosomal DNA were indistinguishable. Comparable findings were obtained following direct examination of the nuclease-sensitive, "spacer" DNA. However, when each chromatin type was fractionated into template-active and -inactive components, it was evident that [(3)H]bromouracil was nonrandomly more concentrated in the template-active portion in comparison to the random distribution of [(3)H]thymine moieties. Furthermore, it was apparent that the template-active chromatin fraction was substantially enriched in the nucleotide sequences of rat DNA known to be sensitive to the virogenic action of BrdU.


Conformational properties of the octanucleotide d(pG-A-T-C-T-T-T-T) and its intermediates.

In studies of some sequence dependent structural factors and stabilizing effects of oligonucleotides the octanucleotide d(pG-A-T-C-T-T-T-T) was of particular interest in view of the presence of an endonuclease cleavage site. Its chemical synthesis is reported as well as the structural effects in CD spectral properties of the octanucleotide and of some related compounds.


Metabolic stability of 2' 5'oligo (A) and activity of 2' 5'oligo (A)-dependent endonuclease in extracts of interferon-treated and control HeLa cells.

Extracts of interferon-treated HeLa cells adsorbed to poly(I) . poly(C)-agarose have been used to synthesize 2'5'oligo(A). This oligonucleotide has been characterized by enzymatic digestion with alkaline phosphatase, snake venom phosphodiesterase, T2 ribonuclease and chromatography on DEAE, and PEI-cellulose. The oligonucleotide inhibits protein synthesis in vitro and activates an endonuclease present in extracts of control and interferon-treated cells. The metabolic stability of 2'5'oligo(A) has been investigated in these cell extracts. The oligonucleotide undergoes rapid degradation, particularly in the absence of ATP and of an energy regenerating system. Furthermore, the 2'5'oligo(A)-activated endonuclease reverts to an inactive state under these conditions, but can be reactivated upon further addition of 2'5'oligo(A). A possible role for the degradation of 2'5'oligo(A) in the mechanism of interferon action is discussed.


Interspersion of highly repetitive DNA with single copy DNA in the genome of the red crab, Geryon quinquedens.

Kinetic analysis of the reassociation of 420 nucleotide (NT) long fragments has shown that essentially all of the repetitive sequences of the DNA of the red crab Geryon quinquedens are highly repetitive. There are negligible amounts of low and intermediate repetitive DNAs. Though atypical of most eukaryotes, this pattern has been observed in all other brachyurans (true crabs) studied (1,2). The major repetitive component is subdivided into short runs of 300 NT and longer runs of greater than 1200 NT while the minor component has an average sequence length of 400 NT. Both components reassociate at rates commonly observed for satellite DNAs. Unique among eukaryotes the organization of the genome includes single copy DNA contiguous to short runs (approximately 300 NT) of both repetitive components. Although patent satellites are not present, subsets of the repetitive DNA have been isolated by either restriction endonuclease digestion or by centrifugation in Ag+ or Hg2+/Cs2SO4 density gradients.


Circular dichroism and DNA secondary structure.

The change in average rotation of the DNA helix has been determined for the transfer from 0.05 M NaCl to 3.0 M CsCl, 6.2 M LiCl and 5.4 M NH4Cl. This work, combined with data at lower salt from other laboratories, allows us to relate the intensity of the CD of DNA at 275 nm directly to the change in the number of base pairs per turn. The change in secondary structure for the transfer of DNA from 0.05 M NaCl (where it is presumably in the B-form) to high salt (where the characteristic CD has been interpreted as corresponding to C-form geometry) is found to be -0.22 (+/- 0.02) base pairs per turn. In the case of mononucleosomes, where the CD indicates the "C-form", the change in secondary structure (including temperature effects) would add -0.31 (+/- 0.03) turns about the histone core to the -1.25 turns estimated from work on SV40 chromatin. Accurate winding angles and molar extinction coefficients were determined for ethidium.


Dietary management of inborn errors of amino acid metabolism.

Individually, inborn errors of amino acid metabolism are rare. Collectively, however, they constitute a significant group of diseases whose number is constantly increasing. Their recognition is important, especially in childhood, because many of these diseases respond well to diet therapy.


Herpes zoster oticus. Uncommon but recognizable cause of facial paralysis.

Three cases of herpes zoster oticus illustrate the manifestations of this relatively uncommon cause of facial paralysis. Topographic analysis, in which functions of facial nerve branches are assessed, helps establish the level of facial nerve involvement. Sequential faradic stimulation testing often is a sensitive prognostic indicator of recovrey of facial nerve function, particularly if nerve excitability persists. A few recent reports support the use of systemic steroid therapy for herpes zoster oticus; opinions vary regarding the efficacy of surgical decompression for facial paralysis. Although general principles cannot be deduced from three cases, each case discussed exemplifies an important aspect of management. The prognostic significance of results of nerve stimulation tests is illustrated by the complete return of facial nerve function in our first patient. Our second patient's response to systemic steroid therapy supports recent reports of the value of such agents in herpes zoster oticus. Partial return of facial nerve function in our third patient two months after onset of paralysis accentuates the importance of a period of observation before a nerve graft or other rehabilitative procedures are undertaken.


Hyperuricemia and gout. A modern approach to diagnosis and treatment.

Diagnosis of gout by crystal identification in synovial fluid is simple and definitive. To treat gout effectively, the physician must determine whether overproduction or underexcretion of uric acid is the underlying mechanism. The acute attack is treated initially with antiinflammatory agents. After the acute phase is controlled, lifelong definitive therapy for hyperuricemia is begun.


Splenomegaly in children. Identifying the cause.

Splenomegaly is usually the result of systemic disease. The differential diagnosis can logically be subdivided into infectious, hematologic, metabolic, vascular, and neoplastic diseases which result in abnormalities of the lymphoid, reticuloendothelial, or vascular components of the spleen. Splenic enlargement increases the risk of traumatic rupture of the spleen. Splenectomy, although indicated in some conditions, does not always relieve the hypersplenic state, and its benefit must be weighed against the hazard of life-threatening episodes of sepsis.


Investigation of poikilocytic normochromic normocytic anemia. 1. Round and elongated forms.

Occasional nonspecific poikilocytes are found in most normal blood smears, but dominance of one or more forms of poikilocytes usually is indicative of a specific anemia or disease in an organ or organ system. For example, stomatocytes are most commonly associated with acute alcoholism, while teardrop cells classically reflect "spent" polycythemia vera or myelofibrosis. The clinical significance of the various round poikilocytes (spherocytes, stomatocytes, target cells) and elongated poikilocytes (ovalocytes and elliptocytes, teardrop cells, sickle cells) is discussed.


Investigation of poikilocytic normochromic normocytic anemia. 2. Spiculated forms.

Spiculated poikilocytes occur in several different forms. Each form is associated with certain types of diseases or conditions. Identification of a dominant form in a blood smear provides a clue to diagnosis. Helmet cells, triangular cells, and schistocytes most commonly suggest disease in the microvasculature. "Bite" cells are usually a product of drug-induced hemolysis. Keratocytes are variants of helmet cells and therefore occur in the same clinical circumstances as helmet cells. Echinocytes are usually artifacts; true echinocytosis is rare and associated mainly with uremia. Acanthocytosis occurs most commonly after splenectomy but may be encountered in severe liver disease.


Drug allergy in clinical practice.

Adverse reactions to pharmacologic agents are becoming more and more common as more drugs are administered to sicker patients. Allergic (immunologic) reactions are difficult to distinguish from idiosyncratic (nonimmunologic) reactions, and reactions that appear to be similar may have entirely different etiologies. Diagnosis of an adverse reaction and identification of its cause require an index of suspicion, familiarity with the drugs being used, knowledge of common reactions to these drugs, and occasionally, challenge with the suspected drug. Specific diagnosis often obviates unnecessary discontinuance of an effective drug.


Urticaria and angioedema. Common clinical problems.

The cause of urticaria and angioedema often is difficult to ascertain. In most cases the conditions are transient, but a chronic idiopathic form does occur and may be intractable. Acute urticaria and angioedema usually result from an IgE-mediated mechanism; success in treatment depends on recognition of the underlying factor. Chronic urticaria may ultimately necessitate use of corticosteroids. Hereditary angioedema is easily differentiated from idiopathic angioedema by the family history and absence of pruritus.


Allergic and nonallergic rhinitis. Diagnosis and management.

The causes of rhinitis are many. Allergic rhinitis is mediated by IgE, and immunotherapy in selected patients is very effective. Immunoglobulins do not seem to play a role in nonallergic rhinitis, and immunotherapy is ineffective. Correct diagnosis spares the patient needless expense, inconvenience, and eventual disappointment.


[Blood lipid level in the initial stages of diabetes mellitus and normal body mass].

The authors studied the blood level of tryglycerides, cholesterol, and free fatty acids (FFA) during glucose tolerance test (GTT) in 30 women with doubtful, and in 36--with diabetic GIT. There proved to be a significant  elevation of the FFA level in the blood serum of persons with a doubtful GTT type and a significant elevation of the FFA, triglycerides, and cholesterol levels in persons with diabetic GGT. The FFA levels reduction curve following glucose load in persons with a doubtful and diabetic GTT proved to be more delayed. Disturbances of lipid metabolism and reduction of adipose tissue insulin sensitivity occured as soon as the early stages of diabetes mellitus. This pointed to the necessity of diabetes mellitus treatment at its early stages for the normalization of metabolic disturbances. Determination of blood lipids level can aid detection of early diabetes mellitus.


[Dynamics of the pancreatic exocrine functional indices in diabetes mellitus under the influence of comprehensive therapy].

The exocrine function of the pancreas was studied in 52 patients suffering from diabetes mellitus by biochemical and radioisotopic methods. The detected enzyme secretion disturbances correlated with the severity of the disease. Complex therapy, including diet, and administration of hypoglycemic drug and angioprotectors led to an improvement of the exocrine function of the pancreas.


[Clinical characteristics of thyrotoxicosis in juvenile patients].

As a result of thorough examination of patients with juvenile and young thyrotoxicosis (14--18, and 19--25 years old, respectively) peculiarities of the clinical picture of this disease were revealed. The onset of the pathological process and of its course at the early developmental stages, and stability of a number of symptoms were characteristic of the disease. Functional disturbances of the cardiovascular system activity were leading in the clinical picture of juvenile thyrotoxicosis. Association between the severity of the disease and the intensity of cardiac pathology, as well as definite changes in the enzymatic function of the liver were revealed. Marked disturbances were found in the blood protein formula.


[Experience with the use of electroroentgenography in the diagnosis of endocrine diseases].

Electroentgenographic examination was carried out in 729 patients with various endocrine diseases. It is believed that electroentgenography with consideration to such features as marginal effect, numerous details, volumetric impression, etc. has at its disposal valuable auxillary diagnostic possibilities in the complex examination of the patients. Analysis of materials demonstrated electroentgenography to be the method of choice in contrastless X-ray diagnosis of changes in the thyroid and mammary glands, and soft tissues of the limbs. Diagnostic information of electroroentgenograms and of film roentgenograms is of about the same value in examination of the cranium, sella turcica, other parts of the bone skeleton, and also of the internal generative organs. The image of the thymus and of the adrenal glands was found to be somewhat less distinct on the electroentgenograms than on the film roentgenograms.


[Dynamics of glucose tolerance in women under many years' observation].

Repeated glucose tolerance (GT) determinations were carried out at various intervals (under 3 years--I, from 3 to 6 years--II, from 6 to 9 years--III, and in 9 and more years--IV) in 964 women on free diet and free regimen. The initial character of GT (normal, suspicious, diabetic) and the duration of intervals between the examinations (I, II, III, IV) determiner its change in repeated examinations. The more pronounced the GT disturbances during the first examination and the longer the intervals between the examinations--the more frequently were GT disturbances of suspicious and diabetic type, and also the manifest diabetes mellitus detected.


[State of the microcirculation in the relatives of diabetes mellitus patients].

The biomicroscopic study of the conjunctival vessels demonstrated microcirculation disturbances in 43.8% of 105 relatives of diabetic patients, and in 8.5% changes of the optic fundus vessels, irrespective of the glucose tolerance test results. There was a statistically significant difference between the total conjunctival index and its partial values in the relatives of diabetic patients in comparison with the control (healthy) group, and in patients with newly diagnosed diabetes mellitus as compared with the control group and with the group of relatives with a normal glucose tolerance test.


[Effect of destruction and stimulation of the amygdaloid nuclei on the sensitivity of the ovaries and uterus of infantile rats to hydrocortisone and desoxycorticosterone].

The effect of destruction and stimulation of the amygdaloid nuclei on the sensitivity of the ovaries and uterus to hydrocortisone and deoxycorticosterone was studied in 190 infantile female albino rats. Administration of the hormones following the action upon the amygdaloid nuclei led to a sharp reduction of the weight of the ovaries and uterus, an increase in the count of compact and vesicular follicles with reduction of their size. Adrenalectomy with the following destruction and stimulation of the amygdaloid nuclei and the hormone administration led to an even greater reduction in weight of the ovaries; as to the count and size of compact and vesicular follicles--it decreased, and the uterus gained weight.


[Comparison of the clinical and immunological indices in children with diabetes mellitus and obesity].

Complex clinical and laboratory research of nonspecific immunobiological reactivity was conducted in 86 children (35 with diabetes mellitus, 25 with obesity, and 26 healthy children), aged from 3 to 14 years. Lysozyme activity and complement titre were studied during the disease. Reduced reactive possibilities of the organism were demonstrated in diabetic children; reduction of these parameters was directly proportional to the severity of the main process and the extent of decompensation. In obese patients the parameters of nonspecific reactivity tests were higher than in healthy children, and glucose tolerance was disturbed; this was apparently connected with stress of the compensatory-defense mechanisms of the organism. A distinct reduction of the parameters in this group of children under the effect of unfavourable factors pointed to exhaustion of the compensatory mechanisms. Obese patients should be referred to the group of children will increased risk, both in respect to diabetes mellitus and to other diseases. The indices under study could  be applied as tests characterizing not only the immunobiological reactivity and the defense-adaptive mechanisms of the organism, but also the severity and phase of the disease.


[Phospholipid makeup and content in various organs of rats with alloxan diabetes].

The phospholipid spectrum and their content in the liver, heart, kidneys and the brain of rats was studied comparatively under normal conditions and in alloxan diabetes. Under pathological conditions there occurred significant changes in the amount of individual phospholipids in all the organs, but the most pronounced changes were noted in the brain. A sharp increase of cardiolipin content and a regular reduction of choline-containing lipids--lecithin and sphyngomyelin--in the organs under study were characteristic of alloxan diabetes. Oscillations in the concentration of other phospholipid fractions (phosphatidyl serine, phosphatidylinositol, phosphatidylethanolamine) had a definite organic specificity.


[Insulin and proinsulin degradation normally and in experimental diabetes].

The authors studied insulin and proinsulin degradation with homogenates of various rat tissues under normal conditions and in alloxan diabetes. The radioimmunological method was used for insulin determination by the decline of immunoreactive insulin and proinsulin from the reaction medium. Homogenates of various normal rat tissues are distributed by their capacity to destroy insulin and proinsulin in the order of decline as follows: the liver, kidneys, muscles, and the epididymal fat. In insulin equimolar quantities proinsulin was destroyed much less than insulin under the same experimental conditions. Alloxan diabetes led to reduction of the capacity of all the tissues homogenates to destroy both insulin and proinsulin. Reduction of degradation was the most pronounced when the muscle and adipose tissue homogenates were used.


[Histophysiology and histopathology of the adrenals in experimental hypokinesia].

In experiments on male rats in the course of 3-month hypokinesia phasic changes were observed in the relative adrenal gland weight, in the volume of the cell nuclei of the glomerular, fasicular zones and the medulla, in the activity of the succinic dehydrogenase, alkaline and acid phosphatases, in the RNA and catecholamine content. These changes are associated with variations in the secretion and biosynthesis of the hormones of the cortical and the medullary layer of the adrenal glands during the hypokinetic stress development.


[Age-related characteristics of the blood supply to the thyroid gland (histochemical and stereological studies)].

Complex histochemical and stereological study of the thyroid gland vessels in A/He mice revealed significant age changes in the organ vascularization, and allowed assessing the dynamics of the relative value of the functioning vessels and of the transport processes activity in the capillary-thyrocyte system at different postnatal ontogenesis stages. There was a low vascularization level the first postnatal days; it increased considerably by the time of sexual maturation, and was followed by a relative stabilization. The organ vascularization decreases with aging chiefly on account of the transport processes reduction in the capillary-thyrocyte system. At the same time, the greatest age variability was characteristic of the relative volume of functioning vessels.


Some structure activity relationships of phencyclidine derivatives as anticholinergic agents in vitro and in vivo.

Phencylidine derivatives exhibit multiple interactions with cholinergic systems: they block nicotinic and muscarinic receptors,and inhibit both acetyl and butyrylcholinesterase. In peripheral tissue, the net pharmacological effects of the phencyclidines is antiacetylcholine activity. The dissociation constants measured in isolated smooth muscle and from competition experiments for the muscarinic high-affinity binding sites in brain homogenates (Kd = 10(-5) - 10(-6) M) are 3--4 orders of magnitude lower than those of anticholinergic glycolate esters. However, phencyclidines have comparable potency to that of d-tubocurarine in blocking the nicotinic receptor in the isolated frog rectus abdominis (Kd = 10(-6) M). Brain uptake experiments of (3H) labeled phencyclidine showed that during the time period in which central effects are observed with these drugs their concentration in brain reaches values close to the Kd (10(-5) - 10(-6) M). This finding, and the cross tolerance observed in vivo between phencyclidine and other centrally acting cholinergic drugs supports the possible involvement of cholinergic interactions in the psychotropic action of phenyclidine derivatives. Quantum chemical calculations of the interaction pharmacophores of drugs in the phencyclidine series have indicated the molecular determinants for the interaction of these drugs with the muscarinic receptor. The calculations revealed that these drugs can match the reactivity characteristics of ACh and the semi-rigid muscarinic agonist 3-acetoxyquinuclidine, but their rigid molecular frame will be conductive to antagonistic rather than agonistic activity when the drug-receptor complex is formed. The identification of a "cholinergic interaction pharmacophore" for these drugs by quantum mechanical calculations made possible the suggestion of other active phencyclidine derivatives, e.g. p-NH2 and p-OH analogs which proved to be equipotent to phencyclidine. The inactivity of the p-NO2 derivative was also predicted on this basis and served as an additional confirmation of the theoretical criterion for activity; the difference between the activities of the ethynyl and cyano derivatives was explained by the modification of the cholinergic interaction pharmacophore. On the basis of these theoretical predictions, electrophysiological studies were carried out by the others and the results prompted the suggestion that "physostigmine is of potential value in the treatment of post-operative patients emerging from ketamine anesthesia and in the treatment of phencyclidine overdosed patients".


Modification of the cardiotoxic effects of ouabain by acepromazine, tetrodotoxin and magnesium sulphate.

Acepromazine (500 microgram), tetrodotoxin (0.5 microgram) and magnesium sulfate (7.5 mg twice) given intracerebroventricularly increased the doses of ouabain given by continuous intravenous infusion, required to induce arrhythmias and death. Acepromazine (150 microgram kg-1) was also effective when administered intravenously. Acepromazine (1.5 mg kg-1) and tetrodotoxin (4-6 microgram kg-1) given intravenously did not protect against, and even increased, the toxicity of ouabain. Both substances decreased blood pressure and increased heart rate. Tetrodotoxin, but neither acepromazine nor magnesium sulphate given intracerebroventricularly, induced a decrease in the heart rate before ouabain infusion. Acepromazine (500 microgram) and tetrodotoxin (0.5 microgram), but not magnesium sulphate, given intracerebroventricularly, decreased the blood pressure before ouabain infusion. The results are discussed in relation to the effects of those substances and ouabain on the circulation, and to the fact that the cardiac arrhythmias induced by high doses of ouabain and the protection obtained with tetrodotoxin and magnesium sulphate are, at least in part, mediated by the central nervous system.


A study of D-glucose uptake by small intestine of rats following in vivo vinblastine treatment.

The pharmacokinetics of tritiated vinblastine in rats has indicated a considerable excretion of the alkaloid through bile into the intestinal lumen. The present study was undertaken to find out whether the presence of the alkaloid in the lumen of small intestine alters the normal transport of nutrients across the small intestine. This was done by measuring the in vitro D-glucose uptake by slices of small intestine of rats pretreated with vinblastine. Vinblastine pretreatment was done by filling the lumen of in vivo segments of small intestine of rats with different concentrations of the alkaloid for 30 and 60 min before uptake was measured. A significant dose-dependent reduction in D-glucose uptake was observed.


Relationship between surface activity and toxicity to Chang liver cultures of tricyclic antidepressants.

Chang liver cell cultures were exposed to the tricyclic antidepressants, chlorimipramine (CIM), nortriptyline (NT), amitriptyline (AT), imipramine (IM), and dosepin (DOX). Loss of enzymes into surrounding media and cytopathic changes were used to quantitate cytotoxicity. Time- and concentration-related cytotoxic effects were evident for all drugs. The order of cytotoxic potency was CIM greater than NT greater than AT greater than IM greater than DOX. All tricyclic antidepressants tested lowered the surface tension of the salt solution contained in the tissue culture media and the order of their surface activity was identical to that of their cytotoxicity. It is postulated that the cellular toxicity induced by tricyclic antidepressants in vitro is related to a function of their surface activity.


Clinical evaluation and care of the insensitive foot.

Until fairly recently, foot deformity was accepted as part of the natural course of a disease with associated sensory loss such as Hansen's disease or diabetes. Now we recognize that most of this deformity is caused by physical forces and that, with proper care, deformity can be prevented. The therapist must perform accurate methods of assessment such as inspecting and palpating the skin, testing for sensory loss, recording footprints, and measuring foot volume and must provide knowledgeable treatment techniques. The patient must be taught how to care for his feet and how to prevent continued trauma with subsequent infection and bony absorption, which ultimately result in deformity that could have been prevented. These evaluation, treatment, and education techniques are discussed in detail.


Temperature assessment of the insensitive foot.

Temperature assessment has proven valuable in detecting areas of inflammation in the insensitive limb. Monitoring the inflammatory response to the stresses of footwear and walking has worked as a "pain substitute." In conjunction with other evaluation methods, the results of temperature assessment can be used to reduce the incidence of injury and ulceration in the insensitive foot. A review of principles and methods, a presentation of a case study, and a discussion will elaborate upon the concepts of temperature assessment.


Therapeutic footwear for the insensitive foot.

The patient with insensitive feet may be injured by poorly fitted or inappropriate footwear. The risk of soft-tissue injury from friction or pressure can be reduced by careful selection and fitting of footwear and frequent evaluation of both footwear and the patient's feet. Concepts, methods, and materials utilized in treating patients with Hansen's disease can be applied to the prevention and treatment of injuries secondary to sensory deficit caused by other conditions. The microcapsule sock test has been used to assess shear forces and pressures that occur while shoes are worn. Test method and interpretation of test results are described.


Microvascular surgery in young children.

We present a series of 8 children, all less than 6 years of age, which demonstrates the feasibility of primary microvascular replantation or reconstruction of amputated or devascularized parts in children. The function and the appearance obtained were excellent, and the potential for growth was maintained. Fortunately, the vessels were larger in these young children than one would expect. It is apparent that in a healthy, stable child, the careful application of microsurgical principles is an excellent method for salvaging devascularized or amputated parts that are vital for function or appearance.


Histopathogenesis of skin and subcutaneous injury induced by adriamycin.

Extravasation of Adriamycin from an intravenous needle or catheter can produce a progressive skin necrosis and deep painful ulceration. The pathological changes which result in this ulceration were studied in a rabbit model. The earliest changes include vascular obliteration and necrobiosis of collagen. At no point were inflammatory cells found to play a primary role.


Comparison of treatment modalities for recurrent basal cell carcinoma.

We studied 97 patients with recurrent basal cell carcinomas; 20 were treated by surgery, 35 by radiation, 40 with chemosurgery, and two patients had no treatment (because their lesions were too far advanced). There was a treatment failure rate of 11 percent for radiation therapy, 12 percent for chemosurgery and 5 percent for surgical excision. Recurrent BCC requires a careful selection of the mode of therapy, aggressive treatment, and careful long-term follow-up. Using these principles, an excellent cure rate can be achieved by all the 3 modes of therapy included in this report.


A fiberscopic study of velopharyngeal closure in patients with operated cleft palates.

We studied the differences in how velopharyngeal closure is learned and obtained by operated cleft palate patients during various activities. Sixty-eight operated cleft palate patients, who had complete closure during swallowing, were examined with the nasopharyngeal fiberscope to determine the extent of velopharyngeal closure while they were producing pressure consonants or vowels, and during blowing. We concluded that the complete closure when producing vowels was the most difficult to obtain, and closure when producing pressure consonants was a little more difficult than that during blowing.


Examination of peripheral nerves with the scanning electron microscope.

The theoretical applications and advantages of the scanning microscope in peripheral nerve research are presented. The internal anatomy of the peripheral nerve can be distinctly examined, and long segments of axons can be examined without the necessity of tedious study of multiple sections. The SEM should make it possible to more readily study the migration of axon sprouts across a repair site. New concepts in teaching and research may develop from the use of this excellent tool.


Experimental microvascular anastomoses in radiated vessels: a study of the patency rate and the histopathology of healing.

A study of microvascular surgery in radiated tissue is presented. The radiation damage to the vessels and its consequence on the histopathology of blood vessel healing is discussed. The main difficulty encountered was the radiation-induced fibrosis in the perivascular tissues. The patency rate in ther arterial anastomoses was unaltered by prior radiation, but the patency rate in the venous anastomoses fell to 54 percent after high doses of prior radiation.


Extra-abdominal desmoid arising from a capsule around a silicone breast implant.

Musculo-aponeurotic fibromatosis is an extremely rare lesion in the breast, only 16 previous cases having been reported. The unilateral tumor in our patient occurred after subcutaneous mastectomy and bilateral placement of implants. The histological evidence suggests that this tumor arose from the capsule surrounding one of the implants.


Clinical consequences of chronic primal scene exposure.

The author presents a phenomenological survey of the symptomatic, characterological, and transference manifestations observed in five male and five female patients who had spent the first three to twelve years of their lives in the parental bedroom. While chronic primal scene exposure is seen in these cases as not having produced any single specific psychopathological sequelae, certain sexual disturbances, split self-representation phenomena, etc., seem to have been primarily (though not solely) determined by these early exposures.


Chance, ambiguity, and psychological mindedness.

The inability to believe in chance occurrences and an intolerance of ambiguity in the external world are often the outward manifestations of poor psychological mindedness. Such attitudes are frequently accompanied by beliefs in the occult and the mystical. It is suggested that these factors be considered when an individual is being evaluated for analytic treatment.


On the concept and consequences of the primal scene.

The concept of the primal scene is in need of redefinition and clarification. The primal scene is not identical with its regressive transformations or later derivatives. Because of the different implications for normal development and for psychopathology, the primal scene as a universal fantasy should be differentiated from the primal scene as real experience. The effects of exposure to the primal scene are considered in relation to the developmental level of the child, other problems in the parent-child relationship, and cultural attitudes.


Mental transitional spheres.

The human being may be considered to have mental transitional spheres in which the sifting, transforming, intensifying, and inhibiting of stimuli are initiated. Stimuli essential to the development of the psychic apparatus are converted in the mental transitional spheres into a form that will enable them to exert the appropriate influence on the ego. Optimal ego development cannot take place without the proper functioning of these spheres. Thus, the mental transitional spheres are essential for the development of psychic functions and defenses.


Skin conductance responsivity during acute episodes of schizophrenia as a predictor of symptomatic improvement.

Skin conductance responses to a series of tones were measured in 41 patients during an acute episode of schizophrenia before they received treatment and after 4 weeks of treatment with either alpha-flupenthixol, beta-flupenthixol or placebo. Patients who did not habituate to the tones prior to treatment tended to show no symptomatic improvement during the course of treatment. Patients who habituated and also showed an acute onset of their current symptoms ('Feighner negative' patients) showed a marked improvement even without active medication. Skin conductance responsivity did not change with improvement in symptoms alone, but decreased in patients on active medication (alpha-flupenthixol). Non-habituation of skin conductance and insidious onset (i.e. fulfilment of the Feighner criteria) were found to be independent predictors of poor outcome. Taken together, these criteria may define a group of patients with particularly poor prognosis.


Corticosteroid and growth hormone responses to methylamphetamine in depressive illness.

It is suggested that, if depressed patients have deficient noradrenergic function at central alpha-adrenergic receptors, then they will also have impaired corticosteroid responses to methylamphetamine but unaltered growth hormone responses. This prediction has been confirmed when the responses of a group of patients with endogenous depression were compared with the responses of a group of patients with other functional psychoses, a group of patients with reactive depression, and a group of patients with other psychiatric diagnoses. These findings support the hypothesis that there is a functional deficiency of noradrenaline at some central alpha-adrenergic receptors.


Multicompartmental analysis of amino acids. III. Tyrosine in affective disorder.

Multicompartmental studies of tyrosine in patients suffering from affective disorders and controls gave estimates of 2 major pools of amino acid, together with the associated fractional clearance rates and fluxes. The 2 pools were considered provisionally to represent extracellular and intracellular tyrosine. The concentration of tyrosine in plasma (representing the extracellular pool) and fractional clearance rates from this compartment were normal in ill and recovered patients. The observed abnormalities were confined to the intracellular compartment and consisted of low concentrations of tyrosine in both depressed and recovered patients. In addition, fractional clearance rates from the intracellular compartment were raised in the depressed patients but had returned to normal after recovery. A comparison of these data with those of a similar study of tryptophan described previously suggested that alterations in compartmental volume or dietary differences could not explain the 2 sets of findings. The disturbances in tryptophan metabolism in unipolar affective disorder had led to reduced amounts of this amino acid in the extracellular space. In contrast, the concentration of tyrosine in this compartment was normal, presumably as a result of a metabolic adjustment to the lower amounts found in the intracellular pool. The presence of illness-dependent and illness-independent alterations in tyrosine metabolism in unipolar affective disorder, together with the earlier findings for tryptophan, may have a bearing on the aetiology of the illness.


A scaled version of the General Health Questionnaire.

This study reports the factor structure of the symptoms comprising the General Health Questionnaire when it is completed in a primary care setting. A shorter, 28-item GHQ is proposed consisting of 4 subscales: somatic symptoms, anxiety and insomnia, social dysfunction and severe depression. Preliminary data concerning the validity of these scales are presented, and the performance of the whole 28-item questionnaire as a screening test is evaluated. The factor structure of the symptomatology is found to be very similar for 3 independent sets of data.


The use of the Visual Analogue Mood and Alert Scales in diagnosing hospitalized affective psychoses.

A consecutive series of 90 admissions of functional patients was examined with the Present State Examination (PSE). Based primarily on PSE findings together with previously published diagnostic criteria, we identified 11 clear or index cases of schizophrenia, 12 of affective psychoses, and 12 of neurotic/personality disorders. All patients were given daily 2 analogue scales, one measuring mood and the other alertness. Among the index cases, the depressives were distinguished by low scores on both scales and the manics by high scores. There was little overlap in the distribution of the scores among the diagnostic groups, suggesting that these scales might be effective psychological markers of clear affective versus clear non-affective functional disorders. Among the undiagnosed cases, those with low or high scores on both scales resembled index affectives phenomenologically, clinically, and demographically. The scores of the 'affective-like' patients overlapped little with those of the 'non-affective-like' patients. The scales therefore might be practical diagnostic aids.


Psychiatrists' models of mental illness and their personal backgrounds.

Seventy-nine junior psychiatrists at the Maudsley Hospital answered 16 biographical questions and a 68-item questionnaire measuring attitudes to the psychoanalytical, biological, social, behavioural, and anti-medical models of mental illness. The psychoanalytical model was the most clearly defined and its adherents the most dogmatic, while those supporting the social model were the most eclectic. Sex, social class, education and political sympathy proved a poor guide to the orientation of the respondent. Individuals who had decided on a career in psychiatry before entering medical school were the most critical of the biological model. Biologically minded psychiatrists were older and, in contrast to Kreitman's findings, there was a shift from a psychoanalytical to a biological preference with increasing psychiatric experience. The importance of scientific attitudes in psychiatry was endorsed by biologically and behaviourally inclined psychiatrists but denigrated by supporters of the analytical approach. Adherents of the psychoanalytical model had as many academic qualifications as the biologically inclined, but had fewer publications and were less active in research. It appears that interest in psychoanalysis is antipathetic to the development of scientific attitudes conducive to research.


The question of hormonal influences on intellectual development: growth hormone.

Contrary to expectations based on findings of enhanced brain development and learning in rats after prenatal growth-hormone administration, a sample of patients with growth-hormone deficiency of early onset did not show impairment of mental abilities when tested with standard intelligence tests. We conclude from our findings, as well as from other clinical reports, that growth-hormone deficiency of onset does probably not interfere with normal human brain development.


Reduced caloric intake following small bowel bypass surgery: a systematic study of possible causes.

Food intake, appetite and a variety of feelings were measured pre- and post-operatively in obese patients undergoing jejuno-ileal bypass surgery. Decreased food intake correlated closely with the amount of weight loss at both 4 and 30 months after surgery. Malabsorption correlated with weight loss at 4 months but not 30 months post-operatively. The cause of the decreased food intake is unknown and cannot be completely explained by either depression, nausea, malabsorption, liver disease, an attempt to avert diarrhoea, or decreased appetite.


Psychological aspects of dialysis: a semantic differential study.

As a consequence of technological advances over the last 15 years, patients suffering from terminal renal failure are now being kept alive for considerable periods of time, either by renal haemodialysis or, where appropriate and possible, by renal transplantation. The former necessarily imposes restrictions on the patients' lives which may be manifest at various levels. The basic aim of the study to be reported was to conduct an exploratory investigation of the psychological impact of dialysis on such patients, together with some of the factors that may influence their reactions to it. Using a Semantic Differential technique, 21 patients on dialysis were compared with a group of 21 healthy control subjects in terms of the personal meaning of selected concepts. Both groups were then subdivided on the basis of age, sex and, in the case of the patients, in terms of length of time on dialysis. Subgroup comparisons were then conducted. The findings suggest various hypotheses which have both theoretical and clinical implications.


The prognostic significance of psychological factors in the management of chronic bronchitis.

Eighty-three chronic obstructive bronchitic patients were psychologically assessed before being randomly allocated to 1 of 3 management regimes. The following measures were taken: psychiatric disturbance, personality, social-desirability response set, vocabulary, expectations about treatment, attitudes and beliefs about bronchitis, effect of patient's bronchitis on the family, work, self, physical exercise, smoking, and general health. Outcome was assessed after one month and again one year later, and the measures included physiological tests of lung functioning, an exercise tolerance test, reported symptoms, time off work, drop-out, and death. Contrary to expectations, it was found that psychological variables had some prognostic significance for outcome assessed by medical measures of illness severity. More important was the finding that, in bronchitics under retiring age, weeks off work during the year of the study could be predicted by psychological variables but not by physiological measures of illness severity.


Psychophysiologic disorders: a critical appraisal of concept and theory illustrated with reference to the irritable bowel syndrome (IBS).

The concept of psychophysiologic disorders and the major theories invented to account for such disorders are critically reviewed. The Irritable Bowel Syndrome (IBS) serves to illustrate the application of each theory and provides a vehicle for their appraisal. The tendency to think of 'physical' and 'psychological' as separate entities rather than separate languages has led to attempts to make a categorical distinction between disorders caused by 'psychological' factors and those caused by 'physical' factors. Some of the theories developed to account for psychophysiologic disorders are unscientific and none can adequately account for all the features of IBS. It is concluded that the concept of psychophysiologic or psychosomatic disorder is outmoded.


Angiographic ablation of parathyroid adenomas.

Six mediastinal parathyroid adenomas were stained by infusing contrast agent through a catheter wedged in the feeding artery. Adenomas in the first three cases were stained unintentionally with small volumes of dilute contrast media and hypercalcemia recurred within 3 to 6 months. In the next three patients, adenomas were deliberately stained with larger doses of concentrated contrast media and these patients have remained normocalcemic from 2 to 18 months following staining. The permanency of parathyroid ablation following deliberate staining with contrast media has not been established.


Reflux esophagitis: radiographic and endoscopic correlation.

Although the value of endoscopy in reflux esophagitis is accepted, the role of radiology has not been well defined. The radiographic and endoscopic findings in 75 patients were correlated. A grading system was employed to stage the severity of involvement. Thirty-five appeared normal on endoscopy and 40 had esophagitis of differing stages of severity. The results indicate that radiography is insensitive in mild degrees of inflammation but that its sensitivity and accuracy improves in more severe grades of esophagitis.


Desirability of roentgen esophageal examination immediately after pneumatic dilatation for achalasia.

Although infrequent, esophageal rupture is a serious complication of pneumatic dilatation for the treatment of achalasia. Because of an experience with delayed recognition of esophageal perforation in a patient with achalasia, we now examine the esophagus using a water-soluble contrast medium immediately following every pneumatic dilatation. This technique allows immediate detection of esophageal perforation.


Duodenal tuberculosis.

Duodenal tuberculosis is a very rare disease and is usually associated with active pulmonary tuberculosis. These patients may present with symptoms and initial radiographic findings of pyloric canal obstruction. Hypotonic duodenography may reveal a submucosal mass with no other specific changes. The lesion is unpredictable. It may respond to medical therapy but it may also progress and require surgical intervention.


Noncalcified echinococcal liver cyst.

A large echinococcal cyst containing clear fluid was seen as a lucent defect within the liver on the plain radiograph. It had no fatty or calcific contents. No similar cases could be found in the literature.


Percutaneous cholecystostomy and cholangiography in patients with obstructive jaundice.

Direct puncture and drainage of the gallbladder were found to be feasible in a patient with obstructive jaundice. The technique appears to be safe and free of major complications, even in patients considered to be extremely poor surgical risks.