Common bile duct perfusion combined with operative cholangiography. A series of 223 patients undergoing cholecystectomy has been studied. In 204 patients the common bile duct was perfused with saline at a pressure of 30 cm. The rate of flow has been analysed as a means of determining the presence of common bile duct stones, this being confirmed on the evidence of operative cholangiography or exploration of the duct. The results suggest that flow studies can be more consistently obtained than cholangiograms, which were not available for technical reasons in 8.0 per cent of patients in this series. The results of flow studies are comparable with those of cholangiography in confirming the normality of the common bile duct but are less reliable in detecting stones. The reliability is such that if radiological facilities are not available, flow studies are an acceptable alternative. In none of these patients was stenosis of the sphincter of Oddi detected. If this clinical entity does exist, it is rare and of little significance.


Disinfection of the skin of the abdomen. The skin of the abdomen of 106 staff and 358 patients was sampled 5 min and 2 h after disinfection using contact plates. Control areas of skin were treated with water only or left untreated. A reduction of 99 per cent (log reduction factor = 2) or more in colony counts was obtained in 5 min with 70 per cent ethyl alcohol and alcoholic solutions of chlorhexidine, povidone-iodine and chloroxylenol/EDTA. Aqueous solutions of chlorhexidine (0.5 per cent) Savlon (5 per cent), povidone-iodine (10 per cent) and chloroxylenol/EDTA (X10 recommended concentration) also showed similar reductions. Weaker aqueous solutions of chlorhexidine (0.05 per cent), Savlon (1 per cent) and chloroxylenol/EDTA (recommended concentration) were significantly less effective than the alcoholic and the most effective aqueous solutions, although all were more effective than water. Total bacterial counts were lower from the skin of female than from male staff and lower from staff than from patients. Pathogens (Staphylococcus aureus or Gram-negative bacilli) were isolated from only one member of staff in small numbers and irregularly and rarely in large numbers from patients. Few pathogens were isolated after application of any of the disinfectants.


Cancer of the rectum following colectomy and ileorectal anastomosis for ulcerative colitis. The case notes of all patients treated for ulcerative colitis by colectomy and ileorectal anastomosis at the Gordon Hospital under the care of Mr S. O. Aylett from 1952 to 1976 have been reviewed. Three hundred and seventy-four patients left hospital with an ileorectal anastomosis and have been followed for periods up to 23 years. Twenty-two patients are known to have developed a carcinoma of the rectum. Within 10 years of the onset of the disease, no rectal carcinoma was found in 3534 patient-years. The risk was 1 in 185 patient-years between the tenth and twentieth years and 1 in 115 patient-years between the twentieth and thirtieth years. The cumulative risk was 6 per cent (+/- 2 per cent) at 20 years and 15 per cent (+/- 4 per cent) at 30 years. The need for meticulous follow-up is emphasized. The finding of dysplasia in rectal mucosal biopsies will, it is hoped, identify the patient at particularly high risk and enable rectal excision to be undertaken before carcinoma develops.


An androgen-associated hepatic adenoma in a trans-sexual. A case is reported of an hepatic adenoma developing in a patient who had been taking testosterone for 3 years. There appears to be an association between various steroid preparations and hepatic neoplasia. Reports of such cases with all relevant data will allow a balanced assessment of the problem to be made.


Congenital solitary cysts of the liver and spleen. Three symptomatic cases of congenital solitary cyst are reported, one in the liver and two in the spleen. Recurrence of the hepatic cyst after partial excision and drainage was complicated by fistula formation between the cyst and the duodenum. The fistula was successfully closed at a second operation. Calcification of the cyst wall occurred in one of two epithelial cysts of the spleen in young women, which were treated by splenectomy. Besides their rarity, congenital solitary cysts of the liver and spleen have several other features in common. Isotopic and ultrasonic scanning assist diagnosis in both conditions.


Progress of acute appendicitis: a study in children. The results of six simple investigations are compared with the duration of the disease in 100 children with acute appendicitis. The results indicate that during the first day on which the appendix becomes inflamed the local defence mechanisms of the appendix are impaired sufficiently to allow invasion by the bacterial organisms in its lumen. This initially inflamed and subsequently infected appendix may develop in the manner indicated. Local and/or generalized complications may follow, i.e. acute appendicitis in its successive stages of development, which may be regarded as (a) inflamed, (b) infected and (c) complicated, and these changes take place at intervals of 1 day. Bacterial and faeoliths are present in the lumen of the appendix, whether inflamed or not, and it is suggested that they complicate the disease rather than being responsible for causing it.


Should you drain a perforated appendix?

Should you drain a perforated appendix? One hundred and three consecutive patients undergoing appendicectomy for perforated appendicitis were randomly allocated either to have an intraperitoneal drain inserted or not. The results of this trial lend no support to the advocates of drainage.


Talc granuloma of the ureter: a case report. A patient presented with symptoms of ureteric colic. At laparotomy a ureteric stricture was found which was presumed to be tuberculous, but histological examination proved it to be a talc granuloma, the talc having been introduced as a glove powder 20 years previously during a hysterectomy operation.


A fundoplication clamp.

A fundoplication clamp. An instrument is described which has been specially designed to facilitate the performance of the operation of fundoplication for the surgical treatment of oesophageal reflux.


Variations in number of births and perinatal mortality by day of week in England and Wales. Analysis of the births that occurred in England and Wales during 1970-6 showed that they followed a seven-day cycle, being concentrated from Tuesdays to Fridays and least numerous on Sundays. This pattern became increasingly pronounced during the period examined. Relatively few births occurred on bank holidays, especially Christmas Day and Boxing Day. In general perinatal mortality was higher among babies born at weekends than among those born on weekdays. It is likely that the pattern seen in the numbers of births is associated to a large extent with elective intervention. It is not possible to draw any conclusions about the pattern seen in perinatal mortality as so far the analysis has been confined to crude rates.


Computed tomography of abdomen in staging and clinical management of lymphoma. During July 1976 to Demember 1977, 150 patients with Hodgkin's disease and 138 with non-Hodgkin's lymphoma were examined by computed tomography (CT). In 45 cases 50 repeat examinations were conducted. Concurrent laparotomy and lymphography were performed on 68 and 56 patients respectively. The overall incidence of false-positive CT examinations as confirmed by laparotomy was 7.4%. In 18 patients with non-Hodgkin's lymphoma in the abdomen there was good correlation between the two techniques. Of the 50 patients with Hodgkin's disease who underwent laparotomy, 17 had splenic disease and 14 minimally enlarged lymph nodes in 20 areas; CT, however, detected only four diseased spleens and five minimally enlarged lymph nodes. Nevertheless, CT often detected enlarged lymph nodes missed by lymphography and was 23% more efficient than lymphography in detecting unsuspected disease. CT also detected unsuspected disease in patients with relapse of lymphoma. CT may replace other non-invasive investigations of abdominal disease in patients with lymphoma and give a reliable guide to  prognosis. It does not, however, eliminate the need for laparotomy in staging Hodgkin's disease.


Visual screening of pre-school children. In an attempt to reduce the incidence of persistent amblyopia and related disorders, routine screening of the visual function of pre-school children has been introduced in Ayrshire, the tests being carried out by orthoptists. A pilot study confirmed the feasibility of the screening. Under the definitive scheme, whose first three months' results are presented, the children are examined as near as possible to their homes and the average attendance rate has been 86%. Thirty-seven of 442 children were referred to an ophthalmic clinic with suspected abnormalities (only one of which was not confirmed) that had not been picked up by the GP or welfare clinic. It is concluded that visual screening of pre-school children is administratively feasible and welcomed by parents, and that it can detect abnormalities missed by traditional procedures-which according to these results may be more than half of the total.


Guar crispbread in the diabetic diet.

Guar crispbread in the diabetic diet. Nine diabetic patients who were receiving various treatments supplemented their normal home diets (two patients) or metabolic ward diets (seven patients) with guar crispbread for five days. Their mean urinary glucose excretion fell significantly by 38% during the last two days. A significant fall in fasting blood glucose concentration of 1.1 +/- 0.4 mmol/1 (19.8 +/- 7.2 mg/100 ml) was seen only in those who took guar after the control period. Over eight weeks' treatment insulin dosage was reduced by 21% in five patients, and home testing showed that glycosuria was reduced by 68% in six patients. Guar crispbread is likely to be a useful adjunct to diabetic treatment irrespective of the type of treatment or insulin dosage used.


Mortality among drug addicts in Greater London. During January 1970 to December 1974, 134 deaths in people aged 10-50 years investigated by coroners in Greater London were recorded as being due to drug addiction. Over three-quarters of the addicts were under 30, and 105 (78%) were male; 55 (41%) were unknown to the Home Office. Barbiturate overdose accounted for over half of the deaths, though two-thirds of these were in people registered as addicts to notifiable drugs. Since the Home Office index is concerned with addiction to one class of drugs only, it fails to reflect accurately the prevalence of all serious forms of addiction. Owing to the continuous change in drug-taking behaviour, however, probably no one method of assessment can provide a complete picture, and thus complementary research methods are essential.


Injuries in Rugby Union football.

Injuries in Rugby Union football. In a prospective study of 185 players attached to 10 British rugby clubs, 151 injuries were recorded among 98 of them (53%) during a single season. Forwards sustained significantly more injuries than backs. The standard of rugby, players' body weights, degree of fitness, and presence of joint hypermobility did not affect the risk of injury. The leg was the most common site of injury. Head and neck injuries were significantly more common when play was static and on wet pitches. Scrummaging accounted for no neck injuries. Almost half the injuries occurred during the last quarter of games. Foul play might have caused as many as 47 (31%) of all reported injuries. Complete eradication of deliberately dangerous play would considerably reduce the high incidence of injuries in this sport.


How should a consultant spend his time?

How should a consultant spend his time? The activities of a whole-time consultant psychiatrist with clinical, teaching, and administrative responsibilities were analysed over six weeks. With the exclusion of time spent on call at night and weekends he worked an average of 57.4 hours a week. Altogether 42.3% of his time was spent on clinical work, 25.5% on general administration, and 24.0% on tutorial activities. Although he discharged his duties as well as might reasonably be expected, his clinical work was thought to have suffered. Postgraduate activities and medical administrations are important in the ultimate care of patients, but the structure of the National Health Service does not enable a consultant to meet all these demands adequately.


Doctors, physiotherapists, and placebo pharmacology. A seminar of physiotherapists studied the psychological aspects of their work. Difficulty with doctors rather than patients was unexpectedly prominent. The following factors were identified as contributing to their dissatisfaction: doctors misused physiotherapy as a placebo in cases of incurable and untreatable disease and mental problems; because they faced questions about diagnosis and prognosis that doctors escaped they learnt to avoid knowing the facts about their patients; using quasiscientific apparatus had tended to replace physical contact; they saw their psychological skill as illicit and unprofessional; and they were uncertain about their role as social workers. Nevertheless, they tended to idealise doctors, which sharpened gratification in collaborative work and helped to alleviate anxiety about death and disease, but tended to reinforce sexual stereotyping and the image of physiotherapy as "unscientific," empirical, and intuititive ("feminine").


Inactivation of gonococci by procaine penicillin in vivo. A pilot study. A pilot study was carried out of 25 male volunteers with gonococcal urethritis. After intramuscular administration of 3 megaunits procaine penicillin and 1 g oral probenecid the urethral culture results for Neisseria gonorrhoeae remained positive up to five hours and thereafter became negative. These results may be useful in providing guidelines for advice on the duration of sexual abstinence following treatment. It is suggested that similar studies should be carried out in women.


Clinical experience in the use of cefuroxime in gonorrhoea. Cefuroxime, a new antibiotic derived from cephalosporin-C which is very stable in the presence of beta-lactamases produced by Gram-negative organisms, was used to treat 856 male patients and 340 female patients with uncomplicated gonorrhoea. In men the drug was used in three different doses, 1.5 g, 1 g, and 750 mg plus 1 g probenecid; in women 1 g and 750 mg cefuroxime plus 1 g probenecid was used. Cure rates ranged from 94.8% to 99.3%. The antibiotic was well tolerated and was free from side effects. Cefuroxime would be a valuable and efficient substitute for penicillin in the treatment of gonorrhoea due to beta-lactamase-producing strains of gonococci.


Management of non-specific urethritis in men. Evaluation of six treatment regimens and effect of other factors including alcohol and sexual intercourse. A trial comparing the efficacy of three different tetracyclines, each in two different dosage regimens, in the treatment of non-specific urethritis is described. There was a significant association between the retreatment rate and sexual intercourse. Age, race, duration of symptoms, previous infection, and indulgence in alcohol did not appear to influence the results whereas treatment of sexual contacts before resumption of sexual intercourse significantly reduced the retreatment rate. Single-dose treatment with doxycycline was shown to be ineffective. Treatment with doxycycline for seven days or triple tetracycline for seven days was less effective than triple tetracycline for 21 days or oxytetracyline for seven or 21 days, all of which gave the same success rate.


A clinical and genetic study of spinal muscular atrophy of adult onset: the autosomal recessive form as a discrete disease entity. A clinical and genetic study of spinal muscular atrophy (SMA) of adult onset is reported. A genetic analysis of all cases of SMA occurring over a ten-year period in North-east England (48 index cases) has shown that chronic proximal SMA of adult onset is a distinct clinical and genetic entity, and is not a variant of the more common and relatively benign late juvenile cases. Nine cases of SMA of adult onset have been studied, occurring in 6 families. The median age of clinical onset was 35 years and the mean age at initial medical presentation was 37 years. The sex ratio was 5:4 (males:females). The condition is relatively benign and there is no evidence to date that life expectancy is shortened; there is usually no premonitory evidence of muscular weakness in early adult life. The muscular involvement is relatively symmetrical and the distal musculature is well preserved; clinical progression of the disease is interrupted by periods of apparent arrest. No patient was able to walk completely unaided twenty years after the initial clinical onset; the median age of patients in the study was 61 years but only one was confined to a wheelchair. In the early stages the recessive form of familial motor neuron disease must be excluded. A segregation analysis of sibs born after index cases was undertaken (segregation ratio of 0.20). This finding is consistent with autosomal recessive inheritance with an extended period during which the disease might initially present. The presence of new dominant mutations cannot be excluded, but is unlikely to account for more than 10% of cases. The carrier rate in the English population is estimated to be 1 in 300, with a gene frequency q = 0.00165. Prevalence is 0.32 per 100,000 in the general population. Empirical risks for genetic counselling are presented.


Long latency event-related components of the auditory evoked potential in dementia. Long-latency auditory evoked potentials were recorded from two groups of patients, with and without dementia, and were compared with those from a population of normal subjects ranging in age from 15 to 76 years. A sequence of tones of two different frequencies (1000 Hz and 2000 Hz) was presented and each patient was asked to count the occurrences of the rare (P = 0.15) tones in the sequence. Evoked potential waveforms were averaged separately for the rare and frequent tone. Of the various evoked potential components elicited by the tones, the P3 component (latency 300-500 ms) was found to be the most sensitive to aging in normal subjects. It was also the only component which could be used to differentiate between the demented patients and the normal subjects or non-demented patients. The non-demented patients did not differ from normal in any waveform measure. The magnitude of the latency change of the P3 component in dementia relative to normal was sufficiently large that it may provide a practical and objective measure of dementia in a clinical setting.


Measurements of visual evoked potentials in Parkinson's disease. Visual evoked potentials elicited by reversing grating patterns were recorded in 35 patients with Parkinson's disease and in 26 controls. The average latency of evoked potentials in patients with Parkinson's disease exceeded by two standard deviations the average of the age-matched control group of other neurological patients. Over two-thirds of all patients with Parkinson's disease had abnormal latency. In these patients latency did not correlate with age. In 5 patients the latency became less prolonged on levodopa therapy, suggesting that catecholaminergic pathways have either indirect or direct effects on the generation of visual evoked potentials. Extrapyramidal connections of the visual cortex, as well as retinal dopaminergic neurons, require further study in Parkinson's disease.


Epileptic brain damage: the role of systemic factors that modify cerebral energy metabolism. The possible role of systemic physiological changes (occurring secondarily during status epilepticus) in the causation of epileptic brain damage has been evaluated in rats. Animals were anaesthetized, paralysed and mechanically ventilated; sustained electrocortical seizure discharges were induced by the intravenous injection of bicuculline, 1.2 mg/kg. After two hours of seizure activity brains were fixed by perfusion for histology. Physiological variables were maintained within certain limits from the end of the initial seizure phase (approximate duration twenty minutes) until two hours after onset of seizure to provide six groups: (1) Standard: mean arterial pressure above 120 mmHg, no hypoxia or hypoglycaemia, rectal temperature close to 37 degrees C. (2) Moderate Hypotension: mean arterial pressure at 70-75 mmHg. (3) Severe Hypotension: mean arterial pressure at 50 mmHg. (4) Hypoxia: arterial oxygen tension at 50 mmHg. (5) Hypoglycaemia: non-fed animals, with blood glucose close to 3.0 mumol/g. (6) Hyperthermia: rectal temperature at 40 degrees C. Microvacuolation and ischaemic cell change were identified by light microscopy in scattered neurons in the cortex (principally in the outer layers) in animals in three groups (Standard, Severe Hypotension and Hyperthermia). Similar neuronal changes were seen in the hippocampus (predominantly in the h1 or Sommer sector) in the Standard and Hyperthermia Groups. It is tentatively proposed that neuronal damage in animals with unrestricted cerebral oxygen and glucose availability is due to oxidative mechanisms in cells with excessively enhanced neuronal activity and that lesions caused by failing energy production do not appear until severe degrees of hypoxia are reached.


Efferent connections of the hippocampus and adjacent regions in the pigeon. In this investigation, the projections of the dorsomedial (viz. hippocampus) and adjacent dorsolateral cortical mantle (viz. parahippocampus) of the pigeon telencephalon were studied with the use of 3H-amino acid radioautography. The results indicate that the fibers which arise from these cortical areas project to the septum. The projection to this structure is topographically organized in a crude manner along the longitudinal axis of the hippocampal complex. Fibers arising from rostral levels of the dorsomedial hippocampal complex project principally to central portions of the precommissural septum and to the nucleus of the diagonal band. Cells situated in the rostral parahippocampal area project to the entire region of the commissural and precommissural septum. Fibers arising from the caudal aspect of the dorsomedial cortical mantle project ipsilaterally to the dorsolateral septum and bilaterally to central portions of the postcommissural septum. However, fibers arising from more lateral parts of cortex terminate ipsilaterally along the entire longitudinal extent of the septum. Other classical projections of the hippocampal formation in the mammal which innervate the hypothalamus and thalamus could not be identified in the present study. Thus, it appears that the projections arising from both the hippocampal formation and adjacent lateral cortices of the pigeon correspond entirely to the precommissural fornix of the mammal.


Efferent connections of the septal area in the pigeon. The efferent connections of the septum in the pigeon were studied with the use of anterograde (3H-leucine autoradiography) and retrograde (horseradish peroxidase histochemistry) transport methods. It was observed that the dorsal septum projects to the lateral hypothalamus, portions of the periventricular hypothalamus, dorsomedial thalamus and midbrain reticular formation. Fibers from the ventral half of the septum (i.e., nucleus of the diagonal band) project to medial and lateral sectors of the hypothalamus, dorsomedial thalamus, lateral habenular nucleus and midbrain tegmentum. In addition, fibers originating from this region also project to the hippocampal and parahippocampal cortices.


Morphological variation in the brain of the marsupial brush-tailed possum, Trichosurus vulpecula. The brush-tailed possum, Trichosurus vulpecula, displays an unusual amount of phenotypic variation within its central nervous system. These variations are expressed in terms of gross brain morphology, as evidenced by the occurrence of both highly lissencephalic and gyrencephalic neocortices in apparently normal adult animals; by displacement and asymmetry of certain internal structures, notably within the ventral thalamic nuclei; and by the inconstant occurrence of at least one cell group within the thalamus. These variations are described and discussed with reference to possible functional, ontogenetic and phylogenetic significance.


Effects of testosterone on the testes of sexually quiescent pheasants: evidence for a negative feedback mechanism. 1. The testicular response of sexually quiescent pheasants to testosterone was studied by injection of testosterone alone and in combination with chicken pituitary extract (CPE) for 20 d. 2. Testosterone alone caused a significant decrease in testicular weight, whereas CPE alone caused a significant increase. In combination testosterone and CPE caused no significant change in testicular weight, suggesting a suppression of the stimulatory effect of CPE by testosterone. The depressive effect of testosterone on testicular weight may be explained on the basis of negative feedback mechanism. 3. CPE alone stimulated the production of spermatogonia and primary spermatocytes whereas testosterone, alone or with CPE, did not elicit such a response. The lack of response of the germinal epithelium to testosterone may indicate the ineffectiveness of the hormone in initiating spermatogenesis in pheasants.


Mean wall thickness of trabecular bone packets in the human iliac crest: changes with age. The mean wall thickness (MWT) of packets of trabecular bone was measured in undecalcified iliac crest bone samples of 36 normal subjects (14 female and 22 male) under polarized light. The mean wall thickness was 49.7 +/- 8.7 microns at a mean age of 50.9 years. There existed a significant decrease of MWT with advancing age. With an appositional rate of 0.72 micron/day, the mean formation time of iliac trabecular bone packets is 69 days. The decrease of MWT with age corresponds to a decrease in bone formation at the basic multicellular unit (BMU) level with aging and can partly explain the physiological senile osteopenia.


Hyaluronate in articular cartilage: age-related changes. Articular cartilage of fetal calves, calves, and steers together with normal and osteoarthrotic human cartilage was analyzed for hyaluronate. The hyaluronate content increased with maturation in healthy tissue, particularly in regions of maximum contact, but was low in diseased cartilage.


Effects of parathyroid hormone on the osteoclastic pool, bone resorption and formation in rat alveolar bone. The osteoclast number and its relation to parathyroid hormone have been studied in rat alveolar bone by quantitative histology and fluorescent labeling. The osteoclast number decreases 60 h after parathyroidectomy and remains constant for the next 132 h. Parathyroid hormone administration to parathyroidectomized animals 96 h after the operation induces an increase in osteoclast number within 12 h to somewhat above those of control animals. The elevated osteoclast counts remain constant for 60 h then rapidly fall over the next 24 h to the level seen in untreated parathyroidectomized animals. As determined by fluorescent labeling, normal alveolar bone resorption and formation were disturbed by parathyroidectomy, such that significant bone formation occurred for only 6 days after surgery, after which a quiescent state followed.


Incorporation of tetracycline into impeded and unimpeded mandibular incisors of the mouse. Twenty-four hours after a tetracycline injection, the unimpeded, and more rapidly erupting, mouse mandibular incisor contained 20% to 44% more tetracycline than the contralateral, uncut incisor. It was concluded that the increased tetracycline incorporation reflected a higher rate of mineralization associated with faster tooth formation in the unimpeded tooth. By measuring the amount of tetracycline which became incorporated at different times after an incisor was shortened, it was possible to investigate an early stage of the response of the incisor to cutting. A significant increase in the capacity of the tooth to incorporate tetracycline was detectable 4 h after shortening the tooth, and this was maximal after another 4 h.


Use of stable 48Ca in the clinical measurement of intestinal calcium absorption. Measurements of intestinal-calcium-absorption efficiency are fundamental for understanding calcium homeostasis in health and disease. Stable calcium isotopes are attractive tracers for such measurements, to avoid excessive radiation exposure to the subject and permit serial studies at short intervals. To realize this, we found it necessary to improve the sensitivity and precision of existing thermal neutron activation analyses for 48Ca. This report describes the details, sensitivity, precision, and accuracy of the improved method, and gives the results of studies in which intravenous 48Ca was used in conjunction with oral 47Ca to measure intestinal-calcium-absorption efficiency in patients.


On the nature of arterial and lung calcifications induced in cattle by Solanum glaucophyllum. The chemical and crystalline composition of the mineral deposited in ossified arterial and lung tissues of cows affected by enteque seco (enteque ossificans) has been investigated. The arterial calcification precedes that of lung. The latter was observed only in animals with a calcification of the aorta above 150 mumoles Ca per gram of wet tissue. The mineral deposited in arterial and lung tissues appeared to be a poorly crystallized apatite; following incineration the diffraction patterns of carbonate apatite and magnesium whitlockite, respectively, were found.


Mechanism of osteoclastic bone resorption: a new hypothesis. Osteoclastic bone resorption involves the solubilization of the mineral salts and the degradation of noncollagen bone matrix and collagen fibrils. As no recognizable collagen fibrils have ever been reported within cytoplasmic vacuoles in osteoclasts, it is generally assumed that the collagen fibrils are digested extracellularly in the resorption zone. The extent to which lysis occurs extracellularly and whether or not the osteoclasts phagocytose the degradation products remain to be established. In the present communication, a hypothesis is presented suggesting the possibility that osteoclastic resorption of bone involves the participation of two different cell types. According to this hypothesis, osteoclastic bone resorption is initiated by osteoclasts that demineralize areas of bone and degrade noncollagen bone matrix. After the osteoclasts have moved away or become partially detached from the demineralized site, the exposed collagen fibrils are phagocytosed by mononuclear, fibroblast-like or monocyte-derived cells.


Quantitative histology of bone: a computerized method of measuring the total mineral content of bone. A comparatively simple quantitative method for assessing bone morphology has been evolved. Microradiographs of thin sections of mandible have been scanned with a Joyce-Loebl double beam recording microdensitometer with a scanning autodensidater attachment, using a white beam. For each image the optical densities for all the pixels (picture elements) were divided into 10 groups. The limits of the division were fixed by the maximum and minimum densities occurring within the image. A computer generated map was produced which indicated the spatial distribution of the pixels within each group to which an arbitrarily chosen shading was attached. The number of pixels within each group is also shown on the map. The computer map was compared with the photomicrograph and, where necessary, the original section. The fractional area of hard tissue was then readily determined using the numerical values of each group of pixels.


Effect of testosterone therapy on bone formation in an osteoporotic hypogonadal male. Osteoporosis has been reported to complicate androgen deficiency in males. Accordingly, we have evaluated an osteoporotic hypogonadal male with bone histomorphometry before and after 6 months of testosterone replacement. Androgen therapy resulted in increases in relative osteoid volum, total osteoid surface, linear extent of bone formation, and bone mineralization. The dramatic histological response to hormonal replacement confirms the importance of androgens in bone modeling and remodeling.


Paget's disease of bone and hyperparathyroidism: coincidence or causal relationship? We studied 173 patients with Paget's disease and 105 patients with hyperparathyroidism. Nine patients were found to have both disorders.


Types of "H2O" in human enamel and in precipitated apatites. Types of "H2O" in human enamel and in precipitated apatites are characterized using X-ray diffraction, infrared (IR) absorption spectroscopic and thermogravimetric analyses. Changes in lattice parameters (principally in the a-axis dimensions) and in the character of the IR absorption bands are correlated with weight losses at pyrolysis temperatures of 100 degrees to 400 degrees C and with effect of rehydration and reignition of previously ignited samples. This study demonstrated that the loss of "H2O" below 200 degrees C is reversible and causes no significant change in the lattice parameter of these apatites, whereas loss of "H2O" between 200 degrees and 400 degrees C is irreversible and causes a contraction in the a-axis dimension. It is proposed that two general types of "H2O" are present in these apatites: (a) adsorbed H2O--characterized by reversibility, thermal instability below 200 degrees C, and lack of effect on lattice parameters; and (b) lattice H2O--characterized by irreversibility, thermal instability between 200 and 400 degrees C, and induction of expansion in the a-axis dimensions of human enamel and precipitated apatites. Lattice H2O is assumed to be due to H2O-for-OH and/or HPO4-for-PO4 substitutions in these apatites. Loss of adsorbed H2O caused sharpening of the OH absorption bands in the spectra of these apatites. Loss of lattice H2O caused the appearance of P-O-P absorption bands (due to the presence of P2O74- group) in precipitated apatites containing small amounts of CO32-.


Intestinal calcium absorption, serum phosphate, and parathyroid hormone in patients with chronic renal failure and osteodystrophy before and during hemodialysis. In 34 patients with chronic renal failure (CRF), fractional 47calcium absorption (Fa47Ca) was measured by an external counting method. A significant correlation was found with impairment of renal function, as expressed by the creatinine clearance. There was also a significant correlation of Fa47Ca with the serum phosphate (SeP) level and of immunoreactive parathyroid hormone (iPTH) with renal function. When the relationship of both SeP and Fa47Ca with creatinine clearance was excluded, no partial correlation between SeP and Fa47Ca appeared to exist. A significant increase of Fa47Ca and serum Ca and a significant decrease of SeP and iPTH were found in 12 patients 2 to 15 months after they were put on intermittent hemodialysis. The possible influence of SeP on intestinal calcium absorption is discussed, and it is suggested that impairment of intestinal absorption of calcium is not a main factor in development of renal osteodystrophy.


Surface area of dental enamel, bone, and hydroxyapatite: chemisorption from solution. The surface areas of three different samples of hydroxyapatite, samples of deproteinized bone, and samples of whole and deproteinized enamel were determined by adsorption of an adduct (the diglycidyl ether of bisphenol A with N-phe-nylglycine) from methylene chloride solution. In all cases, the surface areas of these samples agree well with those obtained by the BET (N2) method.


Effect of chronic low-level cadmium intoxication on the Haversian remodeling system in dogs. This experiment was carried out in order to determine whether the chronic administration of low doses of cadmium resulted in an alteration of the haversian bone remodeling system in dogs. Two pairs of littermate beagles were administered 25 ppm cadmium chloride in their drinking water for 6 months. Four beagles matched for age and sex from the same colony served as controls. By means of fluorescent labeling, we measured haversian bone remodeling parameters according to the techniques described by Frost. Statistical analysis of the results showed significant changes at the 0.01 level in: activation frequency, appositional rates, and number of osteoid seams. At the 0.05 level, significant differences were found in the number of resorption spaces and the bone formation rate. In the absence of other evidence indicative of an alteration in the internal milieu of the dogs, it is concluded that a direct toxic action of cadmium on the mechanisms of activation of cells responsible for the creation and formation of new haversian systems cannot be excluded.


Plasma disappearance of rabbit alpha2HS-glycoprotein and its uptake by bone tissue. Plasma alpha2HS-glycoprotein is specifically accumulated in calcified tissues. In the present studies this glycoprotein was isolated from plasma and after iodination with iodine-125 was injected intravenously into young rabbits. The tissue distribution and plasma disappearance rate of this radioactively labeled material were determined. Of the various tissues studied, bone showed the greatest retention of labeled glycoprotein expressed as percentage of the injected dose per gram tissue relative to the plasma content. The rate of loss of iodinated alpha2HS-glycoprotein from plasma was similar to that of alpha2HS-glycoprotein labeled endogenously by using 14C-glucosamine or 3H-glucosamine. The uptake of exogenously labeled 125I-alpha2HS-glycoprotein into bone tissue expressed as a percentage of the injected dose was similar to that of endogenously labeled 14C-alpha2HS-glycoprotein. These results suggest that the 125I-labeled material can be used to study further the metabolism of alpha2HS-glycoprotein by bone tissue.


Correlation of lysozyme activity with proteoglycan biosynthesis in epiphyseal cartilage. Pig epiphyseal cartilage (proximal ulna epiphysis) previously incubated into vitro in the presence of sodium [35S]sulfate or [3H]thymidine was either analyzed by autoradiography or separated into 9 morphologically defined consecutive layers and investigated for 35S-incorporation into the guanidinium chloride-extractable proteoglycans and for lysozyme activity. The lowest 35S incorporation and lysozyme activity were determined in the zone of resting cells, but there is a consecutive increase in the rate of proteoglycan synthesis and lysozyme activity toward the diaphyseal cartilage-bone junction, with the maximum at the lower columnar cell zone and a sharp reduction of both parameters at the hypertrophic zone. The maxima of 35S incorporation and [3H]thymidine incorporation do not coincide. The guanidinium chloride-soluble proteoglycans exhibit macromolecular polydispersity. Fractions excluded from as well as retarded by Sepharose 2B gel could be separated and were detected in all zones. The results indicate a correlation of proteoglycan biosynthesis and lysozyme activity in epiphyseal cartilage.


Tetracycline double-labeling of iliac trabecular bone in 41 normal adults. A histomorphometric evaluation of the iliac crest trabecular bone remodeling was performed after tetracycline double-labeling in 41 normal Danes (12 males and 29 females) aged 19 to 56 years. The fraction of formative (osteoid covered) and resorptive surfaces was unrelated to age but higher in males than in females (P less than 0.02 and P less than 0.05, respectively). The appositional rate (0.65 +/- 0.12 micrometer/day) was unrelated to age and sex, whereas the fractional labeled surfaces were higher (P less than 0.01) in the males (0.18 +/- 0.08 micrometer2/micrometer2) than in the females (0.12 +/- 0.05 micrometer2/micrometer2), and among the females inversely related to age (R = -0.38, P less than 0.05). The bone formation rate at BMU level (0.50 +/- 0.20 micrometer3/micrometer2/day) was unrelated to sex, but among the females inversely related to age R = -0.49, P less than 0.01). The bone formation rate at tissue level was higher (P less than 0.02) in the males (0.13 +/- 0.07 micrometer3/micrometer2/day) than in the females (0.07 +/- 0.03 micrometer3/micrometer2/day) and among the females inversely correlated to age (R = -0.43, P less than 0.05). the age- and sex-dependent variations in the dynamic parameters underline the importance of a more elaborated normal material.


An immunological comparison of rye and calf histones. The rye and calf histones were fractionated by differential solubility and exclusion chromatography. Antibodies were produced against histones H1, H2A, H2B, and H3 of both species and the extent of cross-reaction was measured by microcomplement fixation. The results allowed the identification of rye histones H2A and H2B. The near structural identity of the H3 histones was confirmed by the small immunological distance which indicated an amino acid difference of less than 2% between rye and calf. The interspecific differences found for both H2A and H2B were greater, the amino acid difference estimated from the immunological distance being between 10 and 20%. H1 gave no immunological cross-reaction, indicating a large (greater than 40%) difference in the structure of this protein in the two species. The extent of variation that a histone fraction shows between plant and animal species is probably related to its role in chromatin organization.


Enzymatic sulfation of steroids. V. Partial purification and some properties of sulfotransferase III, the major glucocorticoid sulfotransferase of liver cytosols from male rats. This manuscript describes purification of sulfotransferase III (STIII), the major hepatic glucocorticoid sulfontransferase of male rats, 77.8 +/- 16 fold from cytosol. This represents a probable 250--345 fold enrichment, compared with homogenates. Purified STIII has a molecular weight of 61 500 +/- 2500 from Sephadex G-100 chromatography. It is markedly activated by 5 mM divalent Ba, Ca, Co, Cr, Mg, Mn, and Ni salts; inhibited stronlgy by 5 mM divalent Zn and Cd; and unaffected by 8 mM ADP, ATP, and AMP. Comparison of the ability of purified STIII to sulfate equimolar cortisol, estradiol-17beta, testosterone, and dehydroepiandrosterone suggests that the enzyme may sulfate glucocorticoid preferentially. However, its cortisol sulfotransferase activity is inhibited by a variety of steroids. Of these, dehydroepiandrosterone, dexamethasone, and progesterone were tested extensively. They were found to be competitive inhibitors. STIII has a sharp pH optimum at pH 6.0 +/- 0.1. However, it is routinely assayed at pH 6.8, as explained in the text. It exhibits a sequential mechanism and Km values of 6.82 +/- 1.2 and 6.28 +/- 0.64 micron for cortisol and 3'-phosphoadenosine-5'-phosphosulfate, respectively. It also possesses essential sulfhydryl groups, as shown by p-hydroxymercuribenzoate inhibition studies.


DNA sequence organization in the common Pacific starfish Pisaster ochraceous. The sequence arrangement of the genomic DNA from the common sea star Pisaster ochraceous has been examined. Reassociation kinetics at DNA fragment lengths of 300 base pairs (bp) indicate the presence of at least three repetitive components in this DNA. The majority of these repetitive sequences are reiterated over the range from 10 to 100's. Approximately one-third of the nucleotides are found in repetitive sequences. Analysis of the reassociation kinetics of 3000-bp DNA fragments demonstrates the interspersion of repetitive and unique DNA sequences. The hyperchromicity of 3000-bp fragments reassociated to low Cot values (the product of moles of nucleotide per litre and time in seconds), and the size distribution of S1 nuclease resistant DNA duplex in these reassociation products, indicate a short-period interspersion pattern in the starfish genome. Repetitive segments (400 +/- 100 bp) are interspersed with longer unique DNA sequences. At a fragment length of 3000 bp the major fraction of the single-copy DNA is found in such an arrangement. In addition to short repetitive segments a substantial portion of the repetitive DNA nucleotides are found in segments excluded by Sepharose CL-2B (greater than or equal to 2000 bp). As much as one-quarter of the repetitive sequence nucleotides can be assigned to long segments.


A graphical method for extracting rate constants from some enzyme-catalyzed reactions not monitored to completion. A large number of enzyme-catalyzed reactions can be described by the equation y = At - B(1 - e-kt), where y is the amount of product formed, A is the slope of the linear portion of the curve, and B is a constant dependent on the mechanism of the reaction. The methods which are generally used to extract the rate constant, k, from absorbance-time data described by this equation require that the reaction be monitored for some 10 to 15 half-lives. We show herein that the rate constant k is readily obtained from a plot of (y'' - y') vs. (y' -y0) where y0, y', and y'' are the values of y at times t, t + deltat, and t + 2deltat. This graphical method is simple, reliable, and requires that the reaction be monitored for only three to five half-lives of the exponential phase of the reaction. We have used this method to measure the rate of activation of a mixed disulfide of papain and 2-nitro-5-mercaptobenzoic acid in the presence of substrate.


Arylalkylamines in the adrenal medulla.

Arylalkylamines in the adrenal medulla. The trace amines p-tyramine, m-tyramine, tryptamine, and phenylethylamine have been determined in the bovine adrenal medulla and the rat adrenal gland by the mass spectrometric integrated ion current technique, using the corresponding deuterated amines as internal standards. In the bovine adrenal medulla, these amines were present at levels ranging from 21.7 ng/g for tryptamine to 37.3 ng/g for phenylethylamine, while in the rat adrenal, they occurred in amounts ranging from 5.2 ng/g for m-tyramine to 11.4 ng/g for tryptamine. In the rat, intraperitoneal administration of pargyline (100 mg/kg) increased the adrenal levels of each of the trace amines. Adrenaline, noradrenaline, and p-tyramine were significantly depleted by reserpine (3 or 10 mg/kg), but the level of m-tyramine was unaffected. It is suggested that the mode of uptake of the tyramine isomers into the adrenal medullary granules may depend on the position of the bydroxyl group relative to the side chain on the aromatic nucleus.


Plasma membrane associated proteins and glycoproteins of a temperature-sensitive hamster cell line (ts 3). Hamster ts 3 cells grown at 32 and at 39 degrees C were compared for (a) cell phenotype and growth rates, (b) sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE) patterns of plasma membrane polypeptides, and (c) distribution of radioactivity in SDS-PAGE of plasma membrane glycopeptides metabolically labeled with [3H]glucosamine and [3H]fucose. It was observed that ts 3 cells growing at 39 degrees C and having a normal phenotype contained increased amounts of a glycopeptide of about 250000 daltons and a polypeptide of about 200000 daltons, as compared with ts 3 cells grown at 32 degrees C and having a transformed phenotype. No other alterations of major significance were observed.


Acetylation of peptidyl-tRNA on rat liver polyribosomes. Some properties of the known NH2-terminal acetylation of peptidyl-tRNA on rat liver polyribosomes were studied. Polyribosomes were incubated with [3H]acetyl-CoA and the products were separated into protein and peptidyl-tRNA fractions by an Ecteola-cellulose column procedure adapted for rapid, routine analysis of many samples, so that the characteristics of acetylation of the two fractions could be determined. Extraction of the polyribosomes with 0.5 MKC1--5mM Mg(OAc)2 solubilized acetyltransferase activity which could catalyze histone acetylation, and the extract when added back to the extracted could catalyze only a slight acetylation of peptidyl-tRNA free in solution isolated from polyribosomes by extraction with EDTA. These observations form the basis of any assay specific for the acetyl-CoA:peptidyl-tRNA N-acetyltransferase which is associated with rat liver polyribosomes.


Mechanism of glucose transfer to steroids by rabbit liver microsomes. The formation of the 3-glucosides of estrone, 17alpha-estradiol, or 17beta-estradiol by washed rabbit liver microsomes in the absence of UDP glucose (UDPG) was increased by the addition of crude lipid extracts of rabbit or pig liver and of dolichol or retinol. The reaction was stimulated by Mn2+, Mg2+, and Ca2+. Direct transfer of glucose to the steroid from added UDPG also occurred by a mechanism which was inhibited by metal ions. The two transferases can be separated from each other into the 105000 g pellet and supernatant respectively by treatment with detergents.


Symposium on trauma for the general surgeon. 1. An accident health care program: the organization and development of regional trauma units. Fifteen thousand deaths, 3 million hospital bed--days and billions of dollars per year are the cost of dealing with accidents in Canada. Our present methods of caring for the seriously injured need revision. The available data on accidents, although extensive, are not sufficiently complete to allow clear definition of the Canadian accident profile. We are unable to explain why Canadians are subject to a 25% greater risk of motor vehicle accidents than are Americans. The development of a Canadian accident health care delivery and audit system is proposed that would provide an improved standard of health care and supply a data base for the advancement of effective programs for accident prevention. The system would include radio-equipped ambulance stations strategically located between regional trauma units, which would be equipped to care for the majority of injured patients. Those severely injured patients who could not be handled by the regional trauma units would be transferred to comprehensive trauma units established in the major referral centres. A trauma registry set up in every province would collect data on each patient and accident to provide an accurate provincial accident profile and a national trauma institute would correlate provincial data.


The general surgeon in the management of patients with multisystem trauma in a community hospital. The general surgeon in a community hospital must assume the role of leader of the trauma team in managing patients with multisystem trauma. Initial resuscitative measures must be instituted to assure cardiopulmonary stability. Following this a complete assessment of the various body systems must be undertaken. The general surgeon will then be in a position to decide whether definitive treatment in the community hospital is possible or whether transfer is required. The basis resources of such a hospital in terms of medical expertise, support staff, laboratory and radiology facilities are all important considerations in making this decision. Most individuals with multisystem trauma can be managed in the community hospital.


Management of critical emergencies in chest trauma. Critical emergency cases of chest trauma are of three types: those caused by blunt trauma, thoracoabdominal injuries and penetrating injuries. The author describes the management of the most commonly encountered lesions in each of these three categories. All lesions resulting from chest trauma should be considered as a critical emergency until proven otherwise.


Management of pancreatic trauma.

Management of pancreatic trauma. The treatment of pancreatic injuries presents the surgeon with unusual diagnostic and therapeutic challenges. Errors in the initial management of patients with injury to the pancreas may lead to life-threatening complications. The author suggests that only by maintaining a constant clinical suspicion of the presence of a pancreatic injury and by performing an orderly exploration of the pancreas when indicated can costly delays in treatment by avoided. A thoughtful approach to pancreatic drainage and resection will ensure optimal surgical care to the injured patient.


Rectal injuries.

Rectal injuries. Injuries to the rectum have always been associated with a high mortality. This was reduced when exteriorization was introduced, particularly when it was combined with prompt and effective resuscitative measures. Experience gained during the Vietnam war demonstrated the considerable benefit of washout of the distal rectal segment. The author describes the course of management he advises. After initial resuscitation, roentgenography of the pelvis and abdomen is necessary. Antibiotics should be administered preoperatively. Through a midline incision the rectal wounds are repaired and a proximal diverting colostomy is performed. The nonfunctioning bowel segment should then be thoroughly washed out. Careful search must be made for associated injuries that require attention.


Tuberculous peritonitis in Manitoba.

Tuberculous peritonitis in Manitoba. Between Jan. 1, 1971 and June 30, 1976 the authors diagnosed tuberculous peritonitis in 17 patients. The basis for the diagnosis was a positive culture for Mycobacterium tuberculosis from the peritoneal fluid or nodules (nine patients) or the presence of caseating granulomas in biopsy specimens of the peritoneum (eight patients). Fifteen of the 17 patients were women. Eleven were North American Indians and eight of them suffered from alcoholism. The predominant symptoms of abdominal pain, progressive abdominal distension and vomiting, and abdominal tenderness on physical examination were present both in alcoholics and in nonalcoholics. However, only the former had demonstrable ascites. The mean time from admission to hospital until establishment of the diagnosis was 8.3 days in six nonalcoholics and 49 days in the alcoholics (P less than 0.01). The delay in making the diagnosis in the patients with alcoholism resulted from a tendency to attribute their fever to alcoholic hepatitis and the ascites to portal hypertension. The mean duration of hospitalization was 160.3 days for the alcoholics and only 41.5 days for the nonalcoholics. Two of the eight alcoholics died, one of hepatic failure and the other, 3 years after the diagnosis of tuberculous peritonitis was made, of miliary tuberculosis.


Squamous cell papilloma of esophagus.

Squamous cell papilloma of esophagus. Squamous cell papilloma of the esophagus is rare. Seven well-documented cases have been reported in the English literature. Three further cases are presented, in one of which symptoms were related to the tumour. Although there is no proof that this lesion is premalignant, coincident cancer must be excluded. In each of the authors' cases, endoscopic removal of the tumour was possible. The etiology of esophageal squamous cell papilloma has not been established.


Assessment of student experiences in technical procedures in surgical clerkship. To determine the amount of exposure to technical procedures received by students at the New Jersey Medical School, Newark, NJ, during their first surgical clerkship, a prospective study was carried out over a 3-year period. Students completing each 12-week clerkship filled in a questionnaire to indicate whether they had received exposure to a series of technical procedures. The study showed that students received relatively little experience in some important, though less commonly employed, techniques. It is therefore recommended that: (a) the instruction in technical procedures be carried out on a planned basis; (b) performance of some routine laboratory tests by students be curtailed to permit more time for technical experience in other areas; and (c) the dog laboratory be utilized for the teaching and practice of surgical procedures.


[Effects of chronic and progressive obstruction of the main pancreatic duct on the epithelium of the ducts and the exocrine pancreatic tissue]. The alarming increase in the number of clinical cases of carcinoma of the pancreas provides the stimulation to search for an experimental model that produces chronic progressive obstruction of the main pancreatic duct. Fifteen mongrel dogs were studied for 1 to 11 weeks. To induce chronic progressive obstruction of the pancreatic duct, a cellophane tape was placed around the main duct adjacent to its entrance into the duodenum and tied over a needle with a diameter identical to that of the duct; the needle was then withdrawn. All minor ducts were identified by pancreatography and then ligated with 2-0 silk. Each animal was followed up by repeated ductal pancreatography and measurements of serum amylase and alkaline phosphatase concentrations. Histologic, histochemical and ultrastructural studies were also performed. On both gross and microscopic examination each animal demonstrated chronic pancreatitis with preservation of the islands of Langerhans. In the early period (4 to 7 days) complete ductal obstruction occurred as demonstrated by pancreatography and by elevated serum values for amylase (264% increase) and alkaline phosphatase (209% increase). In contrast to what is seen after acute ductal ligation, the ductal epithelial cells increased in number and height. At 4 weeks a new collateral ductal system had developed and serum amylase and alkaline phosphatase values had reverted to normal. This model is useful in studying the kinetics of pancreatic ductal regeneration and the pathophysiology associated with chronic pancreatic ductal obstruction.


Efficacy of systemic heparinization in maintaining patency of the incised and cannulated brachial artery. Alternate members of a group of 100 cardiac patients subjected to right and left heart catheterization studies and angiography received 5000 units of heparin intravenously prior to arterial cannulation. There was no instance of arterial occlusion among these 50 patients, while in 6 of the control group the incised brachial artery became occluded. No complications of heparinization were observed. It is recommended that, where no contra- indications exist, all patients subjected to brachial artery incision and cannulation receive systemic anticoagulation.


Percutaneous fine-needle aspiration biopsy of intra-abdominal masses. Percutaneous fine-needle aspiration biopsies were performed in 51 patients with various intra-abdominal masses localized by palpation, radiologic studies, ultrasonography or radioisotope scanning. Biopsy specimens were considered positive for malignant disease in 35 (85%) of the 41 patients with such disease, including 26 (96%) of the 27 with metastases. There was one false-positive diagnosis of malignant disease from the biopsy specimens. Surgery became unnecessary as a result of aspiration biopsy in at least 12 patients. One patient showed evidence of intrahepatic bleeding during liver biopsy but recovered spontaneously, and the liver appeared normal at laparotomy 3 weeks later. Aspiration biopsy is an accurate, relatively painless, inexpensive and safe method of establishing a diagnosis of intraabdominal malignant disease. Considerable experience of the cytologist is necessary for good results.


Pathophysiologic changes in obesity.

Pathophysiologic changes in obesity. Obesity is the common expression of several diverse interacting genetic, familial and environmental factors. In addition to having hypertrophic fat cells because of inordinate triglyceride accumulation, many patients with childhood-onset obesity and those who are massively obese regardless of age at onset have an excessive number of adipocytes. Several endocrinologic and metabolic abnormalities are associated with obesity. Triglyceride formation in and lipid mobilization from hypertrophic adipocytes are exaggerated. The increased availability of free fatty acids to the liver contributes to the excessive synthesis of triglycerides and very-low-density lipoproteins; thus, hypertriglyceridemia is frequently associated with obesity. Hepatic synthesis and biliary excretion of cholesterol are also increased. Most of the excess cholesterol is stored in fat cells. The plasma concentrations of high-density lipoproteins are decreased. Hyperinsulinemia, which is characteristically found in the obese, leads to a decreased number of insulin receptors in target cells. The relative insulin insensitivity of the obese frequently results in glucose intolerance. The endocrinologic and metabolic abnormalities are correctable by an appropriate program of meal planning and physical activity.


Medical complications of obesity.

Medical complications of obesity. Obesity leads to several complications that affect many body systems. This paper focuses mainly on the cardiovascular complications, which include coronary heart disease, cerebrovascular disease and stroke, and congestive heart failure; the last may be secondary not only to advanced coronary atherosclerosis, but also to other pathogenetic factors. The increased frequency of coronary heart disease in the obese is largely attributable to the commonly associated hypertension, diabetes mellitus and lipoprotein abnormalities, rather than the adiposity. The lipoprotein disorders that have a role in atherogenesis are decreased plasma concentrations of high-density lipoproteins and elevated plasma concentrations of low-density lipoproteins. Abnormalities in cholesterol metabolism are responsible for the increased frequency of cholelithiasis in obese persons. The factors that mediate the development of cardiovascular and gallbladder complications are correctable by an appropriate program of meal planning and physical activity.


Protein diets for obesity: metabolic and clinical aspects. The alleged benefits of protein diets remain unproven, since research data on the safety and long-term utility of protein products as the principal or only source of nutrients for weight reduction programs are as yet insufficient. First, it is uncertain whether the decreases in body protein turnover occurring with these diets are consistent with normal function over long periods, though net balance of protein is obtained. Second, the main advantage to the patient is the suppression of appetite by the ketoacidosis, but it is the ketoacidosis that causes many of the untoward effects. Third, the addition of carbohydrate to a protein diet does not mitigate the benefit of the protein and prevents most of the untoward effects. Fourth, there is clearly no advantage of "predigested" proteins (which are generally poorer in quality than normal high-protein foods) except for the psychologic factor of being given "medication" for the "disease" of obesity. Fifth, there is a distinct danger of deficiencies of micronutrients developing with prolonged consumption of unsupplemented diets. Sixth, the cardiac disorders associated with death in persons taking these diets have not been shown to be coincidental rather than a direct consequence of the diets.In the present state of understanding of protein diets, they should be supervised only by specially trained physicians in rigorous multidisciplinary programs, preferably those with ongoing research. Only individuals free from contraindications should be so treated. Until compelling data proving the safety and efficacy of these diets are forthcoming, the general public should be counselled against their use.


Behavioural treatment of obesity.

Behavioural treatment of obesity. Behaviour modification is a promising method of therapy for obesity. Helping the patient to gain control over environmental stimuli and positive reinforcement for the acquisition of appropriate eating and exercise habits are the basis of most treatment programs. While behavioural approaches have, on the average, resulted in greater weight loss than traditional measures during active therapy, responses have been highly variable, and the eventual outcome remains to be established by long-term follow-up studies. The best results are probably achieved with a combination of behavioural therapy and other measures such as a formal exercise program. Since primary prevention may be critical to the overall control of obesity, behavioural approaches may also be applied to young children.


Usefulness of the serum ferritin concentration in the detection of iron deficiency in a general hospital. The efficacy of measuring the transferrin saturation and the serum ferritin concentration to detect iron deficiency was determined under routine conditions in a general hospital. The tests were performed on 100 adult patients who consecutively underwent bone marrow aspiration for the appraisal of a wide range of clinical conditions. The absence of stainable reticuloendothelial iron in smears of the aspirate was used as the benchmark of iron deficiency. Of the 86 patients who were anemic 19 lacked hemosiderin in the bone marrow. The percentage of patients with iron deficiency who were correctly classified by the tests (i.e., the tests' sensitivity) was 84% for the transferrin saturation and 79% for the serum ferritin concentration, and the percentage of patients free of iron deficiency who were correctly classified by the tests (i.e., the tests' specificity) was 63% and 96% respectively. The predictive value of an abnormal (positive) result for the detection of iron deficiency was 39% for the transferrin saturation and 83% for the serum ferritin concentration, whereas the predictive value of a normal or high (negative) result for the exclusion of iron deficiency was 93% and 94% respectively. Measurement of the serum ferritin concentration was superior to measurement of the transferrin saturation only in its specificity. The former is of particular value in clinical settings where the prevalence of iron deficiency is low and conditions that increase the serum ferritin concentration out of proportion to the size of the body iron stores are infrequent.


Patients of internists in hospital outpatient departments and in private practice. To test the contention that patients in outpatient departments and private practices differ, variables were assessed that might affect both the process and the outcome of medical care. Two groups of 60 patients consulting nine Montreal internists who worked in both private practice and in an outpatient department of a university teaching hospital were surveyed. The internists served as their own controls. The two groups of patients were compared for 57 demographic, socioeconomic, access, utilization, attitudinal and current medical status variables. Financial factors were minimized by the existence of universal health insurance. The outpatient group was found to be older, less fluent in English, less likely to be employed, less educated, less wealthy, more dependent on public transportation, more disabled, more likely to use ambulatory services, more anxious about health, and more sceptical about physicians, yet more dependent on them than the private practice group. The outpatient group tended to have more active, significant medical conditions and to receive more prescriptions for medication than the private practice group, in contrast to the national patterns in the practice of internal medicine in the United States. Medical educators, researchers, administrators and providers of health care who have assumed that these two groups of patients are comparable must re-evaluate their practices.


Carcinomatous pseudothyroiditis: a problem in differential diagnosis. A 51-year-old woman presented with a painful, rapidly enlarging thyroid gland. The serum concentrations of the thyroid hormones were initially at the upper limit of normal, and the uptake of radioactive iodine by the thyroid was completely depressed. Although subacute thyroiditis was suspected, a biopsy specimen from the thyroid showed malignant disease and no evidence of inflammation. At the time of right subtotal lobectomy metastatic breast carcinoma was diagnosed. Thus, primary or secondary malignant disease of the thyroid can simulate thyroiditis and present a serious problem in differential diagnosis.


Human blood cells ultrastructural changes and mediator release after exposure to roentgenographic contrast media. Adverse reactions to roentgenographic contrast media (RCM) are associated with the release of mediators including complement components (anaphylatoxins), histamine and serotonin. In an in vitro study of platelets and leukocytes from 20 healthy individuals, RCM-induced release of granules from basophils and platelets was correlated with the release of histamine and serotonin respectively. The release of histamine from basophils was augmented in the presence of exogenous complement; in contrast, the release of serotonin from platelets was not dependent on the addition of exogenous complement. Although individual differences were noted, iothalamate most effectively released serotonin, whereas diatrizoate most effectively released histamine.


Mycetoma caused by Nocardia madurae.

Mycetoma caused by Nocardia madurae. Actinomycotic mycetoma was diagnosed in a woman from Jamaica living in Ontario. This is the first case reported in Canada in which the infection was caused by Nocardia madurae. Despite oral therapy with trimethoprim-sulfamethoxazole, local excision of newly appearing nodules was required periodically for clinical improvement. Laboratory procedures were modified to aid in identification of pathogenic actinomycetes.


Increased blood level of prostaglandin-like substances during cardiopulmonary bypass in the dog. Total heart-lung bypass (TBP) for open-heart surgery is often accompanied by a progressive reduction of systemic blood pressure. Since the lung is the main site of elimination of prostaglandins (PGs) from venous blood, TBP may lead to an increase in blood content of vasodilator PGs. TBP was performed in dogs and blood level of prostaglandinlike substances (PLS) was monitored continuously by a bio-assay method. The concentration of PLS increased during TBP to 0.8 ng.cm(-3) blood (in PGE2 equivalents). Restoration of normal circulation led to the disappearance of PLS from the blood. The increase in PLS during TBP was abolished by indomethacin. This was invariably accompanied by elevation of systemic blood pressure. It is suggested that an increased concentration of vasodilator PLS during TBP may contribute to the hypotension observed in total body perfusion.


Responses of cultured heart cells to procainamide and lignocaine. The effects of procainamide and lignocaine, in concentrations from 10(-6) to 10(-2) mol.litre(-1), on the Na influx and contraction frequency of cultured heart cells were studied. Both drugs produced a prompt, dose-dependent reduction in Na influx which was significant (P less than 0.01) for all concentrations tested. Lignocaine affected only that portion of the Na influx which was also verapamil-sensitive, whereas procainamide suppressed in addition, the verapamil-insensitive influx. In addition both drugs produced a concomitant decrease in the spontaneous contraction frequency of the cells. A close linear correlation (r = 0.99) between verapamil-sensitive Na influx and contraction frequency, in the presence of both procainamide and lignocaine was found. From this, and previous studies indicating a dependency of contraction frequency on the inward verapamil-sensitive Na influx, it is suggested that the drugs modify the automaticity of this preparation by a primary influence on membrane Na exchange.


Functional development of cardiac sympathetic nerves in newborn dogs: evidence for asymmetrical development. The functional development of cardiac sympathetic nerves was investigated in 52 puppies, 1 to 6 weeks of age. The effect of nerve stimulation on refractory period shortening at eight epicardial sites was used as criterion. Zero or minimal effect was observed at the first week of life for all the nerves tested, then a sharp increase of effect was observed at the second week, while at the third week, an unexpected decrease was observed for all nerves. At the fourth week, the effect increased again and remained high for the subsequent weeks. Thus functional sympathetic innervation of the heart is not complete at birth, but continues to develop throughout the first 6 weeks of life, following an irregular pattern of progression. The nonuniform maturation of cardiac nerves coupled with the localised distribution of the nerves may provide a basis for regional sympathetic imbalance and subsequent arrhythmiogenesis in early life.


Monophasic action potentials, electrocardiograms and mechanical performance in normal and ischaemic epicardial segments of the pig ventricle in situ. Few studies report simultaneous electrical and mechanical recordings from the epicardium of intact beating hearts in situ during ischaemia. We use suction to apply transducers and electrodes to areas of the epicardium. This interferes little with its behaviour and allows: i) free mobility over the surface; ii) simultaneous tridirectional length changes to be recorded and summed for an overall impression of mechanical behaviour, iii) detection of changes in direction of movement; iv) simultaneous recordings of monophasic action potential and epicardial ECG. During ischaemia we can detect impaired contraction with dyskinesis and a change in direction of epicardial forces. The action potential duration shortens and we have noted impaired conduction, inexitability and recordings consistent with re-entry leading to ventricular fibrillation.


Percutaneous left ventricular catheterisation with an ultraminiature catheter-tip pressure transducer. Percutaneous left ventricular catheterisation with a 4F (O.D. 1.33 mm) catheter-tip pressure transducer is described. The transducer is small enough so that it can be introduced through a short 4F arterial insertion sheath or a Brockenbrough Trans-septal catheter. Experience in 35 patients suggests that this ultraminiature catheter mounted pressure transducer is a valuable addition to the cardiac catheterisation laboratory.


Vascular permeability to proteins and peptides in the mouse pineal gland. The permeability of fenestrated capillaries in the mouse pineal gland to proteins and peptides was demonstrated by means of ultrastructural tracers. Horseradish peroxidase (HRP) and microperoxidase (MP) were injected intravenously and allowed to circulate for approximately 30 s, 1 min, 5 min, 1 or 2 h. The tissue was then fixed by vascular perfusion or by immersion with aldehydes. In all experiments a pronounced extravasation of HRP and MP occurred. Transendothelial vesicular transport seemed to have occurred across the fenestrated capillaries. The most pronounced tracer labeling of vesicles was found after 1 min of MP- or HRP-circulation. The vesicles were uncoated and more than 70% of the HRP- and MP-containing vesicles exhibited diameters between 50 and 110 nm. Furthermore, three other transcapillary pathways taken by the tracers are suggested: 1) via intercellular junctions, 2) through fenestrae and 3) via channels formed by fusion of vesicles with the luminal and abluminal cell membranes. Based on these results, it is assumed that the capillaries in the mouse pineal gland also permeable to peptides synthesized and secreted by the pineal gland.


Changes in structure of ventral epidermis of Rana ridibunda during metamorphosis. The organisation of the ventral epidermis organisation was followed throughout ontogenesis in Rana ridibunda. Epidermis of tadpoles with 2-3 limbs was organised into two layers: a stratum germinativum consisting of elongated columnar cells, and an outer stratum corneum consisting of two types of cuboid cells. Two types of cells can be distinguished; they are a light (clear) cell and a dark (dense) cell. In the 4-legged tadpoles the stratum corneum cells start to flatten and a replacement layer appeared underneath. A well-defined stratum germinativum is found and within it, epidermal glands. Moulting took place for the first time in tadpoles just before metamorphosis, and a well-organised stratum granulosum was formed still containing the two main types of epidermal glands. The flask cells appear in the juveniles for the first time, greatly increasing in numbers in the adult epidermis.


Selective degeneration of chemosensitive primary sensory neurones induced by capsaicin: glial changes. Capsaicin treatment of newborn rats results in the degeneration of primary sensory neurones involved in the mediation of chemogenic pain. In the present study glial changes following the pharmacologically-induced degeneration of unmyelinated primary afferent fibres terminating in Rexed's laminae I and II of the spinal cord were investigated. Light microscopy revealed an increase in the number of phagocytic glial cells in this area, reaching a maximum at 24 h after the administration of capsaicin; they had almost completely disappeared by 72 h. At the ultrastructural level these cells were characterized by their elongate or irregular nuclei with a pronounced heterochromatin pattern, a moderately dense cytoplasmic matrix, hour-glass shaped mitochondria and very large numbers of heterogeneous dense bodies and lipid droplets. On the basis of these observations, these cells were considered to represent reactive microglial cells engaged in the phagocytosis of degenerated neuronal debris. The possible origin and mode of elimination of these elements from the central nervous tissue is briefly discussed.


Effects of colchicine on ultrastructure of the lactating mammary cell: membrane involvement and stress on the Golgi apparatus. The effects of colchicine on ultrastructure of the lactating mammary cell in the rat and goat were studied by electron microscopy. Changes in tissue of the rat were examined over time (1, 2 and 4 h). The goat gland was evaluated by comparing ultrastructure of tissue at the time of maximum milk flow suppression induced by the drug with that of untreated tissue. Colchicine produced notable changes in the tissue of both species: 1) the secretion of lipid droplets and Golgi vesicle contents (exocytosis) was inhibited and the droplets and vesicles became randomly distributed throughout the cell, 2) the Golgi apparatus was significantly reduced in size, 3) casein and lipid continued to be synthesized as evidenced by greater numbers of secretory vesicles and increased sizes of casein micelles and lipid droplets, 4) secretory vesicles showed a propensity to cluster around lipid droplets, 5) isolated microtubules were found occasionally in the control tissue, ordinarily in the vicinity of the Golgi apparatus, but rarely in the colchicine-treated tissue. These observations indicate that colchicine has two effects leading to suppression of exocytosis in the mammary cell: one involves early interference with capacity of secretory vesicle membranes to fuse and a further effect, related to higher concentrations of colchicine, causes intracellular disorganization and loss of polarity. Microtubules were not seen as directly involved in the mechanisms of exocytosis. The secretion of milk fat globules is coupled to exocytosis and thereby is also inhibited by colchicine.


Myosatellite cells associated with different muscle fibre types in the Atlantic hagfish (Myxine glutinosa, L.). The incidence of myosatellite cells associated with "white" and "red" muscle fibres of the parietal muscle and "red" fibres of the craniovelar muscle was estimated by quantitative electron microscopy in the Atlantic hagfish (Myxine glutinosa, L.). Myosatellite cell nuclei constitute 3, 11 and 23% of the total number of nuclei inside the basal lamina of the three types of muscle fibres, respectively. However, the total number of nuclei is highest in "white" fibres, most of the nuclei belonging to striated muscle cells. Myosatellite cell profiles in transverse sections constitute 23, 41 and 61% of the number of muscle fibre profiles of the three types, respectively. The intervals between adjacent myosatellite cells are approximately 135 micrometer in "white" fibres, approximately 55 micrometer in "red" parietal fibres, and only approximately 25 micrometer in craniovelar fibres. Since craniovelar fibres are also comparatively thin, myosatellite cells constitute a significant fraction of the volume inside the basal lamina in these fibres. The myosatellite cells are approximately 30-50 micrometer long and up to 5 micrometer thick. Some myosatellite cells possess few organelles, whereas others appear to contain many free ribosomes, granular endoplasmic reticulum, prominent Golgi apparatus and lysosome-like bodies.


Immunocytochemical demonstration of somatostatin-containing neurons in the hypothalamus of the domestic mallard. In the hypothalamus of the adult domestic mallard, small to medium-sized perikarya are stained specifically with rabbit antiserum against cyclic somatostatin (PAP technique of Sternberger). The somatostatin-immunoreactive material is located in neurons different from those containing immunoreactive LHRH, vasotocin or mesotocin. Somatostatin-containing perikarya are observed 1) in a chain-like arrangement extending from the area of the median division of the supraoptic nucleus to the caudal end of the paraventricular nucleus; 2) as single cells in the preoptic region; and 3) as a conspicuous formation in the optic tract division of the supraoptic nucleus. In the rostral portion of the median eminence, somatostatin-immunoreactive axons penetrate into the external zone. Fine accessory fiber bundles project to the neural lobe.


Ultrastructural evidence for adrenergic nerve degeneration in the guinea pig uterus during pregnancy. In the guinea pig myometrium, the adrenergic nerves selectively demonstrated at the ultrastructural level after treatment with 5-OH-DA, show varying degree of degeneration during pregnancy. The changes are more extensive in a late gestational stage (40-45 days) than in an early one (20-25 days), and are particularly evident in the uterus overlying the conceptus as compared to the regions between the fetuses. Scattered degenerative changes were also observed in myometrial specimens from virgin animals, but probably reflect the normal continuous turnover of axons.


Ultrastructural localization of radiolabelled L-dopa in the endocrine hypothalamus of the rat. Light and electron microscopic autoradiography has been employed to define the neuroanatomical patterns of uptake and binding of radiolabelled L-dopa in the endocrine hypothalamus of the rat. A dorsomedial continuum of arcuate and periventricular neurons selectively sequester 3HL-dopa 20 min following its intraventricular infusion. By 40 and 60 min following the infusion labelling of neurons is minimal and supports the notion of rapid degradation. Other cell compartments such as tanycytes demonstrate uptake of 3H L-dopa. The ultrastructural localization and distribution of radiolabelled L-dopa (or its metabolites) in the rodent hypothalamus is discussed with respect to mechanisms and cell compartments involved in neuroendocrine regulatory processes.


A comparative ultrastructural study of blood cells from nine insect orders. An ultrastructural study of hemocytes from 9 different insect orders has led to the identification of 8 cell types: (1) Plasmatocytes, whose cytoplasm is filled with small dense lysosomes and large heterogeneous structures, are phagocytic cells. (2) Granulocytes, filled with uniformly electron dense granules, are involved in capsule formation. (3) Coagulocytes, which contain granules and structured globules and which possess a well developed RER, are involved in phagocytosis. (4) Spherule cells are filled with large spherical inclusions. (5) Oenocytoids are large cells with few cytoplasmic organelles. These 5 hemocyte types represent the majority of insect blood cells. (6) Prohemocytes, blastic cells which are one of the stem cells a hemocytes, are very few in number in each species investigated. (7) Thrombocytoids and (8) Prodocytes are restricted to a small number of insect species. The ultrastructural characteristics of these hemocyte types are discussed.


The eyes of mesopelagic crustaceans. III. Thysanopoda tricuspidata (Euphausiacea). The compound eyes of the mesopelagic eupausiid Thysanopoda tricuspidata were investigated by light-, scanning-, and transmission electron microscopy. The eyes are spherical and have a diameter that corresponds to 1/6 of the carapace length. The hexagonal facets have strongly curved outer surfaces. Although there are four crystalline cone cells, only two participate in the formation of the cone, which is 90-120 micrometer long and appears to have a radial gradient of refractive index. The clear zone, separating dioptric structures and retinula, is only 90-120 micrometer wide. In it lie the very large oval nuclei of the seven retinula cells. Directly in front of the 70 micrometer long and 15 micrometer thick rhabdom a lens-like structure of 12 micrometer diameter is developed. This structure, known in only a very few arthropods, seems to be present in all species of Euphausiacea studied to date. It is believed that the rhabdom lens improves near-field vision and absolute light sensitivity. Rod-shaped pigment grains and mitochondria of the tubular type are found in the plasma of retinula cells. The position of the proximal screening pigment as well as the microvillar organization in the rhabdom are indicative of light-adapted material. The orthogonal alignment of rhabdovilli suggests polarization sensitivity. Behind each rabdom there is a cup-shaped homogenous structure of unknown, but possibly optical function. Finally, the structure and the function of the euphysiid eye are reviewed and the functional implications of individual components are discussed.


Regeneration of rabbit calcaneal tendon: a morphological and immunochemical study. The regenerated tissue which fills the gap between the stumps of sectioned and unsutured rabbit calcaneal tendon was studied by immunofluorescence, light and electron microscopy from 2 days to 30 weeks after surgery. In the early stages, the newly formed tissue consisted of few connective tissue cells of variable shape dispersed in an abundant intercellular matrix. At 7 days after tenotomy most of the cells were spindle shaped and arranged along the major tendon axis. They showed a well developed rough endoplasmic reticulum, a prominent Golgi complex and bundles of thin and thick filaments. Moreover, they appeared intensely stained when treated with anti-actin and anti-myosin sera. The bulk of the intercellular matrix consisted of bundles of collagen fibers, mostly arranged parallel to the cells. In the subsequent stages the regenerating tissue became more compact, acquiring the morphological characteristics of tendon tissue. At 30 weeks after tenotomy, however, it did not show yet the typical texture of the normal adult tendon. The tenocytes were more numerous and less uniformly distributed, and contained a greater amount of ergastoplasm and contractile proteins. The collagen fibers were similar in size to those of the neonatal normal tendon and the elastic fibers appeared often immature.


Scanning electron microscopy of the respiratory surfaces of Saccobranchus (= Heteropneustes) fossilis (Bloch). The gill secondary lamellae are generally covered with epithelial cells whose outer surfaces form numerous microvilli. The surface of the primary lamellae is characterised by microridges. A particular type of surface sculpturing seems to be associated with given cell boundaries. Further evidence for the derivation of the air tube and fans which guard its entrance by modification of the basic gill structure has been obtained from both the gross surface architecture and microstructure of the individual cell surfaces. Secondary lamellae are represented by stubby projections which generally have a biserial arrangement. The outer surfaces of the epithelia overlying the capillaries of these respiratory islets are coated with microvilli as in the secondary lamellae. On the other hand, the relatively smooth-surfaced 'lanes' between groups of respiratory islets have a microridged surface similar to that of the primary gill lamellae. It is suggested that previous estimates of surface area, and consequently diffusing capacities of the air-breathing organ, have been low in view of the increased surface, due to both their gross and microstructure. Estimates for gill surface area may need very little correction as the spaces between the microvilli and microridges are probably filled with mucus under normal conditions.


Development of the blood-brain barrier to horseradish peroxidase in the chick embryo. One to 20 mg of horseradish peroxidase (HRP) was injected into the allantoic vein of chick embryos between the 7th to 21st day of incubation and its penetration from blood into the interstitium of cerebellum and spinal cord (upper thoracic) was examined by light and electron microscopy in order to study development of the blood-brain barrier. Until the 12th day of incubation (stage 38) the reaction products, indicating the presence of peroxidase, were distributed in every region of the intercellular spaces in both cerebellum and spinal cord, whereas in 13th and 14th day embryos (stage 39 and 40) they were observed only in the medullary regions. In the embryos after 15th day (stage 41) they filled only the intravascular lumen and some micropinocytotic vesicles in the endothelium. These results show that the blood-brain barrier to HRP develops roughly synchronously in various parts of the central nervous system and evolves independently of neurogenesis, the course of which differs considerably in the cerebellum and spinal cord.


The unit structure of the locust compound eye. 1. The ommatidium or functional unit of the locust compound eye comprises a compound corneal lens, 4 cone cells, 2 primary pigment cells, 16 secondary pigment cells and 8 retinula cells. 2. All retinula cells run the entire length from the cone to the basal lamina, although two, called the proximal cells, only contribute to the lowest third of the rhabdom, and one of either cell 6 or cell 7 on our arbitrary numbering system forms its axon one third the way up the ommatidium. 3. 84% of the 417 ommatidia examined had five cone cell processes. The position of three cone cell processes (cone threads) is almost invariable with respect to numbered retinula cells but the remaining threads can take any of three intercellular locations. 4. The position of these threads correlates with the number of the cell distally displaced from the rhabdom. We suggest that cone thread position in the developing ommatidium determines some features of retinula cells and we propose a simple model to account for this.


The effects of vinblastine on acinar cells of the exorbital lacrimal gland of the rat. The effects of vinblastine treatment on acinar cells of the rat exorbital lacrimal gland were studied by electron microscopy. Experimental animals of both sexes were given single intraperitoneal injections of (1) vinblastine (4 mg/kg body weight) at 1 to 24 h before sacrifice; (2) pilocarpine (20 mg/kg b.w.) for 1 h; or (3) vinblastine for 1 h followed by pilocarpine for 1 h. Vinblastine treatment caused a number of changes including autophagocytosis, formation of intracisternal granules, and alteration of secretory granules. These changes varied in extent and onset between male and female rats. In addition, the Golgi apparatus was reduced in size and dispersed throughout the cytoplasm. Mitotic figures were commonly observed. Moreover, vinblastine inhibited the pilocarpine-stimulated degranulation of the acinar cells. In view of the known anti-microtubular action of vinblastine, these results suggest that microtubules are involved in various aspects of the transport, packaging, and secretion of exportable proteins in the lacrimal gland. Additionally, autophagocytosis and alteration of secretory granules may partially result from the interaction of vinblastine with membranes.


Analysis of intestinal cell proliferation after guanethidine-induced sympathectomy. I. Stathmokinetic, labelling index, mitotic index, and cellular migration studies. Guanethidine-induced sympathectomy in the rat during the neonatal period (injection of 20 microgram/g body weight every 48 h from day of birth until day 14) produces an absolute reduction in the number of sympathetic ganglion cells, but no significant alteration of body weight. Superior cervical ganglia show 79.8% fewer cell bodies at 15 days and 92.3% at 45 days; coeliac ganglia exhibit an 81.0% reduction at 15 days and 89.6% at 45 days in guanethidine-treated rats as compared to normal controls. The sympathetic ganglion cells that remain after treatment have an abnormal morphological appearance with distended mitochondria and depletion of endoplasmic reticulum. Sympathectomy produces a prolongation of the generation cycle time (Tc) as measured by the colchicine-induced mitotic arrest technique, and a decrease in labelling, mitotic, and migration indices. In addition, sympathectomy suppresses the amplitude of the circadian rhythm in mitotic activity. The general suppression of this activity in the intestinal epithelium is more pronounced in the jejunum and ileum than in the duodenum. Variation in the effectiveness of sympathectomy on the inhibition of intestinal cell proliferation may be related to segmental differences in cell proliferation, to segmental differences in innervation, and/or to segmental variation in the effectiveness of guanethidine.


B-cells of the synovial membrane. II. Differentiation during development of the synovial cavity in the mouse. Study of pre- and postnatal development of the metatarsophalangeal joint of the mouse shows that the synovial cavity (SC) forms before any differentiation of the synovial mesenchyme. The primitive cleft results from degradation of a thin vascular mesenchymal layer in direct contact with the chondrogenic layers. Differentiation of the synovial membrane coincides with clarification of the SC (3rd to 6th day of postnatal life). When dilatation of the SC occurs (6th to 8th day), the two intimal cells types (A- and B-cells) are well identified. The B-cells already show typical features at day 6; their content of typical dense secretory vesicles is comparable to that of the adult B-cells at day 13. The specific secretory function of B-cells could be correlated with the particular structure of the intimal interstitial tissue and could account for the origin of some protein(s) of the synovial fluid.


Morphological and functional changes in the tight junctions of the bile canaliculi induced by bile duct ligation. Thin sections after bile duct ligation showed that the depth of tight junctions appeared to increase and that the distance between individual punctate contacts appeared to become irregular and wider than in controls. The freeze fracture replicas clearly demonstrated these changes in the tight junction morphology. Changes were noted most conspicuously in the tight junction three weeks after ligation. Measurements of the junctional morphology in control and ligated specimens showed that the junctional depth had increased two fold in the latter, whereas the number of strands had scarcely changed. Lanthanum tracer experiments showed that the tight junctions did not permit the passage of the tracer in normal nor ligated rats. It was concluded that the mechanism of obstructive jaundice could not be related to changes in junctional morphology causing increased junctional permeability.


Gap junctions coupling photoreceptor axons in the first optic ganglion of the fly. The first optic ganglion of the fly, the lamina ganglionaris, was investigated with the transmission electron microscope for the purpose of demonstrating possible electronic junctions. Within a cartridge, the six short receptor cell axons R1--R6 are extensively coupled by symmetrical gap junctions. This is mainly seen in the distal third of the first synaptic region where none or only a few lateral branches of the centrally lying L-fibres (L1, L2) penetrate the ring of six short receptor fibre endings. Gap junctions as found between R1--R6 are distinguished morphologically from chemically-mediated synapses by the closely apposed cell membranes. They exhibit only a 2--4 nm extracellular cleft. Unlike the chemical synapse the gap junction in the neuropile of the fly appears structurally symmetrical. No such gap junctions are found either between R-fibres and glial cells, interneurons and glial cells, between glial cells and between interneurones themselves, nor between the parallel long receptor axons R7/8, which bypass the lamina outside the cartridge. In accordance with electrophysiological data, it can now be argued that the six short receptor axons R1--R6 are electrically interconnected by symmetrical gap junctions.


Ultrastructure of the ultimobranchial follicles of the laying chicken. The ultimobranchial gland of the laying chicken consists of groups of C cells interspersed among a collection of intercommunicating follicles and ducts of variable size and shape. The epithelium lining this system ranges from squamous to columnar and includes stratified squamous and pseudostratified columnar elements. Four cell types are distinguished in this epithelium: F, mucous, C, and basal cells. F cells show microvilli and microfilaments. Pinocytotic activity and images of fusion of coated vesicles with the plasma membrane are evident. The rough-surfaced endoplasmic reticulum (RER) and the Golgi complex are moderately developed. Dense bodies are encountered apically in some cells. Mucous cells possess microvilli and secretory material in the typical form of partially fused droplets. C cells contain secretory granules and are invariably separated from the follicular lumen by other cell types. The smaller, pyramidal basal cells contain filaments, RER, small Golgi complexes, free ribosomes and hemidesmosomes. The lumina contain flocculent or granular material, cellular debris and desquamated cells. Morphological evidence demonstrates that features of the pharyngeal epithelium are retained and that the majority of the cell types, with the exception of C cells, are presumably nonendocrine.