Genotoxicity and cell transformation studies with sorbates in Syrian hamster embryo fibroblasts.

Sorbic acid, sodium sorbate and potassium sorbate were tested for their genotoxic potential in the Syrian hamster embryo (SHE) fibroblast micronucleus assay and the SHE cell transformation test in vitro. Sorbic acid and potassium sorbate showed no activity in either test system. When freshly prepared sodium sorbate solutions were used, no genotoxic or cell-transforming activity was detected. However, sodium sorbate as stored solution, which previously had been heated and sonicated to facilitate solubilization, yielded a positive response in both test systems. It is concluded that oxidation products of sodium sorbate that possess genotoxic and cell-transforming properties are formed under conditions of heating, sonication and storage.


Lack of carcinogenicity of tragacanth gum in B6C3F1 mice.

Tragacanth gum was administered at dietary levels of 0 (control), 1.25 and 5.0% to groups of 50 male and 50 female B6C3F1 mice for 96 wk after which all animals were maintained on a basal diet without tragacanth gum for a further 10 wk. Mean body weights of females in the 5.0% and 1.25% groups were lower than those of the controls after 11 and 16 wk, respectively. However, there were no treatment-related clinical signs or adverse effects on survival rate, urinalysis, haematology, blood biochemistry and organ weight. While detailed histopathology revealed the development of squamous cell hyperplasias, papillomas and one carcinoma in the forestomach, there was no significant treatment-related increase in the incidence of any preneoplastic or neoplastic lesion. Thus, under the experimental conditions used, tragacanth gum was not carcinogenic in B6C3F1 mice of either sex.


Inhibitory effect of carbohydrates on the formation of mutagens in fried beef patties.

Beef patties were prepared by mixing minced meat with water and either glucose (1, 2 or 4%), lactose (1, 2 or 4%) or powdered milk (2, 4 or 8%) before frying. In another experiment, minced meat was mixed with starch from golden bread crumbs (3%) or potatoes (4%), with and without glucose (1, 2 or 4%). The patties (100 g) were fried for 3 min at 150 or 180 degrees C in a double-sided fryer. The mutagenic activity in the crust was determined using the Ames test. With the addition of glucose or lactose (1-4%), the mutagenic activity was inhibited by 34-76%. A similar inhibition of the mutagenic activity was obtained with powdered milk. However, starch from golden bread crumbs or potatoes caused only a slight (not significant) decrease in mutagenic activity whereas adding both starch and glucose to the beef patties inhibited mutagenic activity by up to 54%.


Absence of genotoxicity of potato alkaloids alpha-chaconine, alpha-solanine and solanidine in the Ames Salmonella and adult and foetal erythrocyte micronucleus assays.

To assess whether reported toxicities of potato-derived glycoalkaloids could be the result of interactions with cellular DNA, the genotoxic effects of alpha-solanine, alpha-chaconine and solanidine were studied, using the Ames test (Salmonella strains TA98 and TA100), the mouse peripheral blood micronucleus test and the mouse transplacental micronucleus test. The Ames test for mutagenicity with alpha-solanine was weakly positive in TA100 with S-9 activation (29 revertants per millimole per plate). However, pooled data from duplicate tests gave a negative effect. Pooled data from two experiments with alpha-chaconine gave a weak positive response in TA98 without microsomes (17 revertants per millimole per plate). The micronucleus tests for clastogenicity using male mouse and foetal blood were negative. The absence of mutagenicity and clastogenicity suggests lack of damage to intracellular DNA for potato alkaloid toxicity.


Effects of dietary lipids on whole-body retention and organ distribution of organic and inorganic mercury in mice.

The effect has been investigated of dietary lipids on the whole-body retention and organ distribution of organic and inorganic mercury in mice. A single oral dose of methylmercury chloride or mercuric chloride labelled with 203Hg was given to female NMRI mice fed semi-synthetic diets containing varying amounts (5, 10, 20 or 50%) of energy derived from lipid (coconut oil, soya oil, or cod liver oil). The whole-body retention and relative organ distribution of mercury depended on diet composition. Thus, a significant reduction of the whole-body retention of mercury was seen in mice fed a diet containing 50% cod liver oil compared with mice fed a diet containing 50% coconut oil. After oral administration of mercuric chloride the relative deposition of mercury in the kidneys increased while that in the liver decreased with increasing concentrations of soya oil or coconut oil in the diet. The whole-body retention of mercury after treatment with methylmercury chloride was significantly decreased in mice fed cod liver oil compared with mice fed coconut oil; there was no difference between mice fed cod liver oil and those fed soya oil. The relative disposition of mercury was significantly higher in all organs of mice fed a diet containing 20% energy from cod liver oil compared with mice fed a diet containing 20% energy from soya oil. The present study demonstrates that diet composition is of major importance to the toxicokinetics of methylmercury and mercuric mercury.


Effect of dietary cholestyramine on the elimination pattern of ochratoxin A in rats.

Three experiments with rats established the effects of dietary cholestyramine on the disposition of ochratoxin A (OA) and its hydrolysed metabolite, alpha-ochratoxin (O alpha). In the first experiment OA (1 mg/kg) was incorporated into a diet that contained 0, 0.5, 1.0 and 2.0% cholestyramine. Cholestyramine markedly reduced blood concentrations of OA (1.6 to 0.75 micrograms/ml, P less than 0.0001) for all concentrations of the resin. The second experiment demonstrated that 2% cholestyramine added to the diet of rats markedly reduced cumulative urinary OA excretion (26 to 6 micrograms, P less than 0.01) and increased cumulative faecal OA excretion (8 to 38 micrograms, P less than 0.001). The third experiment established the efficacy of cholestyramine (2%) when added to diets containing two concentrations (0 and 6%) of a saturated fat (tallow). The bioavailability of OA as determined by area under the blood concentration curve over 216 hr was 424 micrograms/ml/hr for the control rats and 186 micrograms/ml/hr for the cholestyramine-treated rats (P less than 0.0001). Cholestyramine treatment increased the recovery of OA plus O alpha in the faeces plus urine over a 5-day period from 65.5 to 96.2% (P less than 0.0001). Cholestyramine also greatly increased the amount of OA plus O alpha and particularly of OA excretion in the faeces (105 to 160 micrograms, P less than 0.0001 for OA plus O alpha and 82 to 150 micrograms, P less than 0.0001 for OA) and resulted in a corresponding decrease in the excretion of these compounds in the urine. The concentration of fat in the diet had a much less dramatic effect than cholestyramine, was mainly detected in the urine and was affected by an interaction with cholestyramine (P less than 0.0001). Cholestyramine greatly reduced the concentration of OA plus O alpha (37 v. 8 micrograms) when the content of dietary fat was low but to a much lesser degree when it was high (19 v. 12 micrograms). These results suggest that the concentration of fat in the diet may affect the pattern of OA excretion in the urine. Cholestyramine added to the diet greatly increases the amount of OA eliminated in the faeces and reduces the amount in the urine, and as a result it decreases the amount present in the systemic circulation.


Effect of subchronic bis(tri-n-butyltin)oxide (TBTO) oral administration on haematological parameters in monkeys: a preliminary report.

A preliminary study was conducted on adult male crab-eating monkeys (Macaca fascicularis) orally exposed to bis(tri-n-butyltin)oxide (TBTO) at doses of 0 and 160 micrograms/kg/day, 6 days/wk, for 22 wk. No treatment-related signs of toxicity or changes in body weight gain were detected during the course of the study. The haematological analyses performed every 2 wk indicated a decrease in total leucocyte count in the treated animals with significant values in wk 8, 10 and 22 of treatment. No differences from controls were noted in clinical chemistry and total tin concentration in blood. These preliminary data on the toxicity of TBTO in the primate model are intended to be an initial contribution towards a better evaluation of the potential toxicological hazard of TBTO to humans.


Effect of prototypic polychlorinated biphenyls on hepatic and renal vitamin contents and on drug-metabolizing enzymes in rats fed diets containing low or high levels of retinyl palmitate.

Two groups of weanling male Sprague-Dawley rats fed a diet supplemented with either 0.6 or 6 retinol equivalents/g diet were each separated into three further groups receiving 300 mumol 2,2',4,4',5,5'-hexachlorobiphenyl/kg body weight, 300 mumol 3,3',4,4'-tetrachlorobiphenyl kg/body weight or vehicle only (corn oil). Only the coplanar (3,4)2Cl congener caused a slight reduction in food intake, thymic atrophy and led to a significant decrease in the liver vitamin A storage. The vitamin A lost by the liver was approximately the same in both dietary groups; however an increased renal accumulation of vitamin A was observed in the high vitamin A group. Serum retinol was reduced by (3,4)2Cl treatment but remained unchanged by (2,4,5)2Cl exposure. Total amounts of ascorbic acid and its oxidation products were increased in the liver and in the kidney by both xenobiotics while niacin and thiamine concentrations were lowered by (3,4)2Cl only. Microsomes from vitamin A-deficient rats exhibited a marked decrease in the anisotropy parameter. After (2,4,5)2Cl exposure, an increase in membrane fluidity was observed linked to a decrease in cholesterol/phospholipid (C/P) ratio. Treatment with (3,4)2Cl caused a significant decrease in the index of fluorescence polarization only in the low vitamin A group even if the C/P ratio was enhanced in both dietary groups. This study shows that the polychlorinated biphenyl with the 3-methylcholanthrene-type pattern of induction of cytochrome P-450 has more profound effects on B group vitamins and particularly vitamin A homeostasis than does the phenobarbital-type inducer. Moreover, this situation, which has been found to be similar to that in vitamin A deficiency, is not ameliorated by a high dietary vitamin A intake.


Is dietary ergotamine atherogenic in the rabbit?

The effect of dietary ergotamine on pre-lesional indicators of atherosclerosis was studied in rabbits. The experimental purified diets contained 0.08% (w/w) cholesterol and either 0, 40 or 200 mg ergotamine-tartrate/kg. After 6 wk, serum total cholesterol concentration and the ratio of serum total cholesterol: high-density lipoprotein-cholesterol were significantly increased by ergotamine in a dose-dependent manner. Dietary ergotamine raised the total level of glycosaminoglycans and the relative proportion of chondroitin sulphate in the abdominal aorta. It is suggested that dietary ergotamine is atherogenic in the rabbit.


Long-term follow-up of the Conaxial (Beck-Steffee) total ankle arthroplasty.

Between 1975 and 1977, 30 patients with traumatic arthritis or rheumatoid arthritis underwent 36 Conaxial (Beck-Steffee) ankle replacements (DePuy, Warsaw, IN). Thirty-two were primary replacements and four were revisions of previous ankle arthroplasties. Twelve patients had traumatic osteoarthritis and 18 patients had rheumatoid arthritis. The average age at operation of patients with rheumatoid arthritis was 61 years (range 28-67 years) and with osteoarthritis was 52.9 years (range 32-72 years). The average follow-up was 10.8 years, with a range of 10 to 13 years. Early postoperative complications included wound dehiscence in 39% of patients (14 patients), deep wound infection in 6%, fractures of the medial or lateral malleolus in 22%, and painful talofibular impingement in 14%. At 2-year follow-up, 27% of the ankle replacements were loose. Sixty percent were loose at 5 years and 90% were loose at the 10-year follow-up. Ten patients had implant removal and attempted fusion. Six, or 60%, fused in an average of 5 months. Of those patients who achieved ankle fusion, four had internal fixation and iliac crest autografting, one had a Charnley compression apparatus with allograft bone, and one had internal fixation with allograft bone. The constrained Conaxial ankle replacement should no longer be implanted because of a 90% loosening rate at 10 years and an overall complication rate of 60%.


Ankle arthrodesis: a long-term study.

Few studies of ankle arthrodesis have assessed tarsal mobility. This study was performed to evaluate radiographically the effect of ankle arthrodesis on tarsal motion. Thirty patients (31 ankles) returned for clinical and radiographic examination, review of charts, and completion of questionnaire forms. Radiographs were evaluated for success of fusion, position of fusion, tarsal motion, hindfoot position, and subtalar and midtarsal arthritis. The median follow-up time was 7.0 years (range 2-20 years). Results showed that fusion was achieved in 22 patients (71%). The evaluation score based on the grading system of Mazur et al. correlated with success of fusion and patient satisfaction. However, no correlation existed between evaluation score and tarsal motion or position of fusion in the sagittal or coronal planes. Radiographic evaluation showed no significant difference between tarsal motion of the fused side and the unfused side. Tarsal mobility was not affected by ankle arthrodesis or by the techniques performed to achieve fusion.


Talonavicular arthrodesis in the rheumatoid foot.

Arthrodesis of the talonavicular joint with a cylindrical dowel was performed in 19 feet in 17 rheumatoid patients with arthritic destruction of the talonavicular joint, but without fixed hindfoot deformity. Osseous union was achieved in 12 feet, but all patients experienced pain relief and no foot showed progressive valgus deformity of the hindfoot during follow-up. Staple fixation seemed to promote osseous union. The procedure, easy to perform and requiring only 6 weeks of immobilization, may, in the absence of fixed hindfoot deformity, supersede triple arthrodesis in rheumatoid patients with hindfoot arthritis.


Hallux valgus correction with proximal metatarsal osteotomy: two-year follow-up.

We evaluated the results of 33 feet in 23 patients who underwent a basilar crescentic osteotomy with a modified McBride procedure with a minimum 24-month follow-up. The average hallux valgus improved from 37.5 degrees to 13.8 degrees and the intermetatarsal 1-2 angle from 14.9 degrees to 4.7 degrees. The angle of declination of the first metatarsal was found to have dorsiflexed an average of 6.2 degrees. Unfortunately, osteotomies secured with staples dorsiflexed to a greater degree. Bilateral foot surgery produced results similar to those with unilateral procedures. Four of our patients developed a hallux varus (range 2-8 degrees); however, none were dissatisfied at the time of evaluation. Although this bunion procedure resulted in more prolonged swelling and pain than a distal osteotomy, it should be considered for more complex deformities to avoid the failure that a distal metatarsal osteotomy might produce given a high 1-2 intermetatarsal angle or a high hallux valgus angle.


Excision arthroplasty for hallux valgus in the elderly: a comparison between the Keller and modified Mayo operations.

A retrospective clinical and radiological review of 51 patients (mean age 66 years) was performed to assess the outcome of excision arthroplasty for hallux valgus in an elderly population and to compare the results of the Keller, which is still used frequently in many centers in the United Kingdom, and modified Mayo operations. Although significant correction of the deformity was obtained with both procedures, this was incomplete and the mean residual hallux valgus angle was greater than 20 degrees. Lateral metatarsalgia was present in over 40% of patients. Both procedures provided good pain relief, and considerable narrowing of the forefoot was obtained with the modified Mayo operation. Excision arthroplasty in the elderly should be reserved for the low demand patient with symptomatic degenerative changes in the first MP joint in the absence of lateral metatarsalgia.


Adult acquired flatfoot deformity at the talonavicular joint: reconstruction of the spring ligament in an in vitro model.

The mobile unilateral flatfoot deformity of chronic posterior tibial tendon insufficiency has been difficult to correct by soft tissue procedures. The procedures can decrease pain, but they do not always correct the longitudinal arch or relieve all the symptoms. Using 10 fresh frozen cadaveric specimens and a rig for stimulation of weightbearing, the deformity associated with chronic posterior tibial tendon insufficiency was produced by multiple ligamentous release and documented by AP and lateral radiographs. Reconstruction of the spring ligament using a ligament bone autograft from the superficial deltoid ligament was then performed and tested under load. The mean correction was within 2.5 degrees of normal (over or undercorrection) on both the AP and lateral radiographs with the specimens under load. Clinical Relevance. In posterior tibial tendon insufficiency, it may be possible to address the ligament as well as tendon insufficiency to gain a corrected arch. The success of such a procedure will depend upon adequate tendon and ligament reconstruction in a fully mobile deformity. Questions remain as to the adequacy of this ligament graft, and a stronger free ligament graft, as well as correction of any bony malalignment, may be required.


An investigation into pellet dispersion ballistics.

Existing works on pellet dispersion ballistics are confined to some data-based models derived from statistical analysis of observed patterns on targets but the underlying process causing the dispersion lacks due attention. The present article delves into the relatively unexplored areas of dispersion phenomena, and attempts to develop a theoretical model for general application. The radial velocity distribution of pellets has been worked out by probing into the physical process of dispersion based on transfer of momentum from undispersed shot mass to dispersed pellets. The ratio 2u/v0 (u = root mean square (r.m.s.) radial velocity and v0 = muzzle velocity of the pellets) is found to be fairly constant for a fixed gun-ammunition combination and has been suitably designated as 'Dispersion Index' (DI) characterising its dispersion capability. The present model adequately accounts for pellet distribution on targets and it appears that 'Effective Shot Dispersion' (ESD) as introduced by Mattoo and Nabar [ESD = [(4/N0)sigma Ri2]1/2, where N(0) is the total number of pellets and Ri is the radial distance of the i-th pellet from centre of pattern], gives a faithful numerical measure of overall dispersion at a given distance. A relationship between ESD and firing distance, incorporating the effects of air resistance and gravity has been worked out, which reveals that DI controls the dispersion at a given distance. For small distances (less than 20 m) the relation reduces to a linear one, as already observed empirically and looks like ESD = E0+DI x firing distance, E0 being a parameter dependent on gun and ammunition. The present model, unlike earlier ones, is versatile enough to explain the natures of the dependence of dispersion on firing distance as well as on gun-ammunition parameters, which are essential for a faithful reconstruction of a crime scene. The model has been tested with such experimental data as are available and reasonable agreement is observed.


SEM analysis of red blood cells in aged human bloodstains.

Mammal red blood cells (RBC) in bloodstains have been previously detected by light microscopy on stone tools from as early as 100,000 +/- 25,000 years ago. In order to evaluate the degree of morphological preservation of erythrocytes in bloodstains, an accidental human blood smear on white chert and several experimental bloodstains on hard substrates (the same stone-white chert; another type of stone-graywacke; a non-stone support-stainless steel), were stored in a room, in non-sterile and fluctuating conditions, for lengths of time ranging from 3 to 18 months. Afterwards, the specimens were coated with gold and examined by a Cambridge Stereoscan 120 scanning electron microscope. Results revealed a high preservation of RBC integrity, with the maintenance of several discocytary shapes, a low tendency to echinocytosis and a frequent appearance of a moon-like erythrocytary shape in the thinner areas of the bloodstains.


Rapists' behaviour: a three aspect model as a basis for analysis and the identification of serial crime.

In this paper it is proposed that the behaviour of an offender during a sexual assault can be considered as consisting of three main groupings or 'aspects'. These have been termed 'Modus Operandi', 'Sexual and Personal Gratification' and 'Attitude and Intimacy'. Although an oversimplification, such a model facilitates a preliminary description of the offender which can be of direct assistance to an investigating officer. Various factors affect the consistency and variability of behaviour and the model has formed a basis for the development of a concept as to which behaviours might be the more useful for identifying linked offences. This more systematic approach to the investigative and intelligence processes is reliant on a victim's statement containing very detailed information about the offender's actions, together with a record of as much of his speech as can be recollected. The material required is described using the model and the text is illustrated with case examples. Instances are quoted of the possible inferences and their relevance to the investigation of sexual offences.


Calcaneal spurs in a black African population.

The radiological incidence of calcaneal spurs in a black African population was studied. Our findings show that spur incidence increased with age and was greater in females than in males. These results, the first from a large, exclusively African population, are similar to those from previous studies of individuals from other continents.


Discrepancy between estimated and actual time elapsed after death of a severed head.

A severed head which had been wrapped in seven plastic bags and set in concrete in an airtight insulated plastic box was found approximately 22 months after the occurrence of death. Ammonium magnesium phosphate had formed and on the basis of this and other observed postmortem changes, time elapsed after death was estimated to be from 2 weeks to 6 months. The absence of oxygen is thought to have contributed significantly to the great discrepancy between estimated and actual time elapsed after death.


Coalition of the hallux sesamoids: a case report.

Multiple variations in partition of the hallux sesamoids have been described; however, to our knowledge, a coalition of the hallux sesamoids has never been presented. A case of coalition of the hallux sesamoids is presented and the literature is reviewed with respect to the possible significance of this anomaly.


Sex allocation of skeletal material by analysis of the proximal tibia.

In this study we contrasted the confidence with which individuals may be grouped and then reallocated on the basis of a set of measurements from the proximal tibia. The data were derived from 100 Caucasoid (50 male) and 102 Negro (50 male) tibia housed in the R.A. Dart Collection. Multivariate discrimination was effected by means of canonical and stepwise discriminant analyses, whilst probabalistic models were used to allocate individuals. High levels of correct classification (84.62-92%) were matched by high levels of reallocation, suggesting that, in contrast to dental or craniobasal measurements, those of the proximal tibia may be usefully employed to allocate an individual on the basis of sex.


The pneumatic ankle tourniquet with ankle block anesthesia for foot surgery.

The use of a pneumatic ankle tourniquet applied to the supramalleolar ankle region is a useful method of obtaining a bloodless field in surgery of the foot. The pneumatic ankle tourniquet allows for more accurate and reproducible control of circumferential compression than the standard Esmarch bandage, when used in conjunction with the regional ankle block. Between March 1987 and October 1990, 84 foot surgeries were performed using the pneumatic tourniquet and ankle block technique on 76 patients by one surgeon. Tourniquet ischemia lasted from 30 to 105 min. Tourniquet pressure was set to 100 to 150 mm of mercury above systolic blood pressure without exceeding 325 mm of mercury. Two patients reported mild pain directly beneath the tourniquet after 45 and 70 min, respectively. Neither patient required deflation of the tourniquet to complete the procedure. The clinical and electrophysiologic evidence showed that no neurologic or vascular damage occurs. The use of the pneumatic tourniquet in conjunction with regional ankle block anesthesia provides a reasonable alternative to the standard thigh tourniquet for surgery of the foot.


Range of motion of the foot as a function of age.

Movement of the foot is essential for human locomotion. The purpose of this paper was to quantify the range of motion of the foot as a function of age and to compare the rage of motion measurements for the foot in a laboratory coordinate system and a coordinate system fixed to the tibia. The measurements were taken in vivo using a range of motion instrument developed by Allinger (University of Calgary, Canada, 1990) from 121 subjects. The results suggest that: (1) the range of motion in general is greater for women than for men in the young adult group; (2) the range of motion in general is in the same order of magnitude for women and men in the oldest age group; and (3) the range of motion is about 8 degrees smaller in dorsiflexion and about 8 degrees higher in plantarflexion for women than for men in the oldest age group. It is speculated that physical activity and common shoe wear are factors influencing the age- and gender-dependent differences in range of motion. Furthermore, it has been shown that the range of motion values measured in a laboratory coordinate system and in a coordinate system fixed in the tibia are different in all directions except inversion. The differences in plantarflexion and dorsiflexion and inversion and eversion are relatively small. However, they are substantial for adduction and abduction. In all cases, the results were bigger for measurements in the laboratory coordinate system compared with the tibia coordinate system, because the movement of the lower leg was included in the measurements in the laboratory coordinate system.(ABSTRACT TRUNCATED AT 250 WORDS)


A fatal case of poisoning with cantharidin.

A case of fatal poisoning due to voluntary ingestion of cantharides powder for aphrodisiac purposes is reported. Clinical history, autopsy and analytical findings are described. Blood and urine samples collected during the 30 h of survival, as well as the cantharides product, were analyzed by gas chromatography-mass spectrometry. On the basis of the percentage of the active principle measured in the powder, an ingested dose of 26-45 mg of cantharidin could be estimated.


An exceptional case of lethal disulfiram-alcohol reaction.

A case of fatal disulfiram-alcohol reaction due to ingestion of ethanol and antabuse is presented. Unusual autopsy findings and toxicological results are described. This case represents a report of corrosion lesion in the lower oesophagus and stomach due to a violent chemical reaction in situ and also the highest blood concentration of acetaldehyde (41 mg/l) ever recorded.


Death by greyhound.

We present the case of a man who was last seen leaving to feed his greyhound dogs. He was found dead lying in a yard just outside the gate to one of the dog pens. Holes were present in the fence on both sides of the gate. The holes were of sufficient size to allow the passage of the head and neck of a greyhound to the shoulders. To open the gate one had to bend down to unfasten a latch 45 cm above ground level. Leaning down to unfasten the latch brought one into close proximity to the holes on either side of the gate. The scene and clothing appeared undisturbed. Autopsy (K.A.L.) revealed the cause of death to be blunt throat trauma. The throat trauma was of marked degree and consistent with at least a single heavy crushing injury directed from the front and somewhat below. In addition there were a series of almost vertical light abrasions on one side of the neck. There were minimal injuries to the rest of the body. There were no injuries specific for assault. In an attempt to explain the almost vertical abrasions on the side of the neck, the scene was re-examined by the pathologist. This revealed loose wire strands on the gate post. It is consistent that a fall against this area could account for the almost vertical abrasions on one side of the neck.(ABSTRACT TRUNCATED AT 250 WORDS)


The microvasculature of the sesamoid complex: its clinical significance.

The microvascular anatomy of the sesamoid complex was investigated in 15 cadaver specimens using histology and tissue clearing (Spalteholz) techniques. It was found that both sesamoids appeared equally well vascularized and the vascular supply to each sesamoid originated from two major sources (proximal and plantar) and one minor source (distal). Proximally, vessels originating from the first plantar metatarsal artery enter the sesamoid at its attachment to the flexor hallucis brevis. In addition, vessels enter the plantar surface of the sesamoid near the midline and arborize throughout the bone, anastamosing with the proximal vessels. The distal vascular supply to the sesamoids originates from its distal capsular attachment and appears to contribute minimally to the overall vascular scheme. The lateral attachments of the sesamoids to the plantar plate and joint capsule were relatively avascular. In two bipartite specimens examined, the major blood supply originated from the proximal and distal poles of the sesamoid. No vessels were observed entering the plantar surface of these specimens. The results of this study suggest that injury to the proximal or plantar aspects of the sesamoids could disrupt the vascular supply to these bones. These areas should, therefore, be avoided during the surgical approach to the sesamoids.


Firearm fatalities.

One hundred and twenty eight cases of shooting fatalities were investigated during an 11-year period. Of these 57% were homicidal shootings with 34% suicidal in nature. Only two suicidal fatalities were female. Analysis of the sites of entrance wounds confirmed the 'sites of election' in suicidal shootings, whilst homicidal wounds showed a much wider distribution. Multiple entrance wounds were seen in 42% of homicidal shootings. Injuries to hands were seen in 7 homicidal fatalities.


Identification of the skeletal remains of Josef Mengele by DNA analysis.

There has been considerable controversy over the identity of the skeletal remains exhumed in Brazil in 1985 and believed to be those of Dr Josef Mengele, the Auschwitz 'Angel of Death'. Bone DNA analysis was therefore conducted in an attempt to provide independent evidence of identity. Trace amounts of highly degraded human DNA were successfully extracted from the shaft of the femur. Despite the presence of a potent inhibitor of DNA amplification, microsatellite alleles could be reproducibly amplified from the femur DNA. Comparison of the femur DNA with DNA from Josef Mengele's son and wife revealed a bone genotype across 10 different loci fully compatible with paternity of Mengele's son. Less than 1 in 1800 Caucasian individuals unrelated to Mengele's son would by chance show full paternal inclusion. DNA analysis therefore provides very strong independent evidence that the remains exhumed from Brazil are indeed those of Josef Mengele.


Retinal hemorrhages: replicating the clinician's view of the eye.

The authors describe a technique for the gross examination of postmortem eyes of children who are suspected to have been the victims of deliberate trauma. By removing the anterior segment (cornea, iris, lens and pars plicata of the ciliary body) en bloc by a coronal incision through the pars plana just anterior to the ora serrata, the pathologist may view and photograph the fundus exactly as it would have been seen clinically. The photographs obtained with this technique correlate more closely with antemortem clinical examinations and photographs than conventional gross examination procedures and have been introduced as evidence in trials concerning the issue of retinal hemorrhages in injured children. The anterior segment and optic nerve are also examined to facilitate a comprehensive description of ocular findings.


Sudden unexpected death due to Taxus poisoning. A report of five cases, with review of the literature.

The toxicity of yew (Taxus) has been known since antiquity. However, in the past 31 years, to our knowledge only six cases of Taxus poisoning have been reported in the literature. In the present paper we add five cases. From a forensic point of view, intoxication with Taxus has three important aspects: (i) the clinical presentation, which among other causes should suggest Taxus intoxication; (ii) the fact that the diagnosis may often be easily made by examination of the contents of stomach, duodenum and small bowel and (iii) the widespread availability in the near future of Taxol, an anti-neoplastic drug which is an alkaloid extracted from Taxus. The clinical and autopsy findings are summarized, the diagnostic aspects are discussed and the literature concerning Taxus is reviewed.


[Iatrogenic origin of pleural effusion. A rare complication of the central venous catheter].

A 47-year-old woman with unremarkable plain chest X-rays in whom the Seldinger technique was employed to place a central venous line via the jugular vein, a catheter-related pleural effusion developed. This case points up the need to exercise care when placing a central venous line, and suggests the need to use contrast medium for the radiological follow-up examination.


[Diagnosis of female urinary incontinence. Progress with urodynamic functional diagnosis].

Owing to its frequency and severe consequences for the women affected, urinary incontinence poses a considerable problem. Our knowledge about its pathophysiology, as also the diagnostic and therapeutic possibilities, remain remarkably limited. The main types of incontinence are stress, urge, reflex and overflow incontinence. Other forms are rare. A major diagnostic and therapeutic problem is posed by the mixed type, which can account for up to 60 percent. Owing to the morphologically and functionally complex nature of the lower urinary tract, the diagnostic approach to incontinence must involve various levels, and comprises careful history taking, a thorough physical examination, and special urodynamic evaluation. Abundant therapeutic approaches, both pharmacological and surgical, are available, but opinion as to what constitutes the best therapeutic concept varies greatly. Despite the only moderate chances of successful treatment under realistic conditions, our present knowledge about the diagnosis and treatment of female urinary incontinence needs to become more widespread.


[Isotretinoin treatment of acne conglobata. Andrologic follow-up].

Twenty patients (21.4 +/- 4.3 years) with extensive acne conglobata affecting the face, chest and back, were treated for a period of six months with isotretinoin (13-cis retinoic acid, 13-cis RA) at a dosage of 1 mg/kg body weight/day (mean daily dose 72.7 +/- 9.8 mg 13-cis RA). In all cases, the acne conglobata cleared up completely. With the exception of symptoms produced by mucocutaneous exsiccation, no side effects were observed; the laboratory parameters were all within normal limits during the anti-acne treatment phase. There was no recurrence of the disease within a period of one year after cessation of treatment (n = 13). Screening spermatograms performed at two-month intervals during the treatment phase revealed, from the fourth month of treatment onward, a statistically significant increase in the mean sperm density with sperm morphology and motility unchanged as compared with the situation prior to treatment. One year after conclusion of treatment, all measured spermatogram parameters had returned to the initial values. The investigations revealed no evidence of any negative influence of the 6-month treatment with isotretinoin on spermatogenesis.


[Renal cell carcinoma--diagnosis, differential diagnosis and prognosis].

Consideration of the approach to the diagnosis and differential diagnosis of renal cell carcinoma and the criteria needed for an assessment of prognosis. Thanks to the comprehensive use of ultrasonography and abdominal CT, asymptomatic renal cell carcinomas confined within the renal capsule are now more often being discovered and treated by curative surgery. With the aid of ultrasonography, abdominal CT and NMR imaging, pre-operative visualization of tumor spread is now better, although, with the exception of angiomyolipoma, it is still not possible to adequately differentiate the rare benign tumors of the kidney, for example oncocytoma, from renal cell carcinomas with these procedures. The TNM classification permits a highly differentiated prognostic classification of the renal cell carcinomas. The additional prognostic parameters, triploidy and hypertetraploidy determinable by flow cytophotometry, are also considered. Early detection of renal cell carcinomas in an asymptomatic stage decisively influences the further prognosis, so that for all upper abdominal ultrasonographic explorations, performed for whatever reason, attention should be paid to such incidental findings.


[Concepts in surgical therapy of kidney cancer].

Three new aspects of the operative treatment of renal cell carcinoma can be made out: 1. for the removal of tumor thrombus extending to the right atrium, the surgical technique of choice involves whole-body hypothermia and extra-corporeal circulation. Only in this way can these tumors be removed completely under good vision. 2. Provided the patient's contralateral kidney is healthy, even small peripheral renal tumors should be submitted to radical nephrectomy. The rate of concomitant small tumors is reported to be as high as 20, while the recurrent rate associated with local incision is just on 7%, and the risk of carcinomas developing in the contralateral kidney is only 1.8-3.8%. 3. Radical nephrectomy for tumor should continue to include the ipsilateral adrenal gland. Although in our own patients the incidence of simultaneous adrenal metastasis was only 1.4%, if the adrenal gland is left in situ, part of the renal capsule also has to be left behind, and the upper pole of the kidney dissected free, with the associated risk of disseminating tumor cells.


[Effect of nilvadipine on diurnal blood pressure profile. Use of a new calcium channel blocker in mild to intermediate hypertension].

QUERY: Influence of Nilvadipine, a new calcium channel blocker on the daytime blood pressure profile and 24-hour blood pressure values in patients with mild-to-moderate hypertension. Single-blind study in 20 hospitalized hypertensives over a period of 23 days (10 days placebo, 8 days 1 x 8 mg Nilvadipine, 5 days placebo). Blood pressure was measured at 7.00 a.m. prior to drug ingestion and daytime blood pressure profiles obtained on days 10, 11, 18, 19 and 23. The objectives were to lower the median diastolic blood pressure or daytime blood pressure profiles on the last day vis-a-vis the baseline values, and to establish the response rate (blood pressure diastolic less than 90 mmHg) 24 hours after the last dose of Nilvadipine. After 8 days on Nilvadipine, the median diastolic daytime blood pressure profile had decreased by almost 10 mmHg. The response rate was 42%. In the same period, the systolic blood pressure decreased by 30 mmHg. Six out of 20 patients manifested transient side effects typical of calcium channel blockers.


[Ambulatory cataract operation--a new concept becomes established].

Outpatient cataract surgery, in particular employing phacoemulsification, has now become established practice in Germany. It is as safe as the inpatient procedure but for most cataract patients less stressful, cheaper and associated with shorter waiting lists. As experience in more than 2,500 cases has shown, the outpatient procedure is fully acceptable--also with respect to complications.


[Recognizing and treating suicidal behavior. Part 1. Results of scientific suicide research, relevant for general practice].

Whatever his specialty, every medical practitioner will at some time encounter patients at risk of suicide. Medical research into suicide has produced a wealth of knowledge with which the practitioner should be familiar if he is to provide such patients with adequate care. Great importance attaches to a knowledge of groups at a particularly high risk, of motivations, and of the phases of psychodynamic development leading to a suicidal crisis. On the basis of the particular features of the suicide risk, the family doctor, who is often consulted shortly before an attempt at suicide is enabled to recognize the mental distress of the patient.


[Self-instruction expert systems in medicine. Presentation of knowledge, acquisition of knowledge, prediction of suicide as an example].

1. Description of how self-learning expert systems work, and 2. comparison of various algorithms for the establishment of a data base for suicide prediction. from exemplary patient data, self-learning expert systems obtain their expert knowledge which they subsequently employ to establish the diagnosis in new patients. Various possibilities of storing knowledge may be employed, for example the decision tree, classes of rules or neuronal networks. The various forms of representing knowledge are also presented. Taking the prediction of suicidal risk as an example, the effectiveness of the algorithm is tested with the aid of a patient questionnaire. Different fields of application require different systems. The diagnosis of such expert systems can at least prompt the care-providing physician to reconsider his own diagnosis.


[Prevention of coronary heart disease by therapy of hyperlipidemia. Between cholesterol hysteria and therapeutic realism].

The present paper is intended to provide an overview of the arguments for and against drug treatment of hyperlipidemia. An argument in support of lipid-lowering prophylactic and therapeutic programs is the close relationship between lipid levels and coronary heart disease, which has been documented both epidemiologically and by interventional studies. Arguments against comprehensive treatment of hyperlipidemia have to do with the fact that although large interventional studies have shown a reduction in mortality from coronary heart disease, there has been no reduction in overall mortality. Of decisive importance for the decision to apply lipid-lowering treatment is the overall risk profile of the patient concerned. This includes not only pathological lipid levels, but also numerous other factors that must be taken into account when considering the indication. Whether to initiate lipid-lowering treatment or not should be determined on the basis of the individual patient's risk profile, with additional consideration being given to age and sex.


[Recognition and treatment of suicidal risk. Part 2: Diagnostic and therapeutic procedure in medical practice].

The knowledge gained by medical suicide research and clinical experience provides a practical basis for diagnostic and therapeutic guidelines for the care providing physician. Practical approach: The danger of suicide can be estimated on the basis of mental abnormalities and the health or social situation, and the level of risk approximately assessed. The appropriate therapeutic approach is determined in talks with the patient, which often decide his/her subsequent fate and that of the immediate family. The question as to whether to refer the patient to institutional psychiatric care--a step that should rarely have to be taken against the patient's will--must be carefully considered. The provision of care to suicidal patients on an outpatient basis requires from the physician a high level of knowledge, sensitivity and commitment that goes beyond mere specialized expertise.


[TENS: fiction and fact].

TENS (transcutaneous electrical nerve stimulation) is a widely used therapeutic principle that is aimed at ameliorating pain of various genesis. Its effectiveness had been more or less accepted, when a study denying this very point was published and gave rise to considerable international uncertainty. The result was general rejection of TENS (at least in the USA). This reaction is, however, certainly not justified. An analysis of the international literature shows that most original data are favorable to TENS. It is to be hoped that the matter will again receive intensive international research and that within a few years we will have identified the indications for this form of therapy.


[Effect of acarbose on injection-eating interval in type I diabetes. Preliminary contribution].

In a pilot study, 7 patients with Type I diabetes received three daily doses of 100 mg acarbose for three days within the framework of intensified insulin therapy. At the same time, the 30 minute interval normally observed between injection and eating was abandoned. The blood glucose levels measured one hour post-prandial in diabetics taking acarbose and not observing the injection-eating interval were lower than those measured prior to acarbose and while observing the interval. Large-scale controlled studies are needed to investigated the theory that in insulin-dependent diabetics taking acarbose, observation of the injection-eating interval can be abandoned.


[Ambulatory follow-up care in laparoscopic cholecystectomy].

FUNDAMENTAL CONSIDERATIONS: With increasing frequency, laparoscopic procedures are now replacing conventional cholecystectomy. Given the choice, patients with cholecystolithiasis almost always opt for the former procedure. Because the laparoscopic procedure offers considerable advantages as compared with open surgery, the increased risk of local complications associated with it tends to be ignored. For example, injuries to the biliary ducts are about ten times as common as in the case of conventional cholecystectomy. Injuries to the bowel, previously unknown, are increasingly being observed. Symptoms associated with undetected injuries usually do not occur until the patient has been discharged. Ambulatory aftercare is particularly important following laparoscopic cholecystectomy. Complications need to be detected in good time in order to be able to institute appropriate counter-measures.


[Methodological deficiencies in clinical trials].

In many cases, the results obtained with clinical trials are out of all proportion to the time, money and effort invested by those participating in them. The reasons for this are to be sought, for the most part, in readily avoidable errors at the planning stage, during evaluation and during preparation for publication. Common weak points prove to be the design of the trial, patient numbers, selection of end points, characteristics of case material, blinding, randomization, exclusion from evaluation, test efficiency (power 1-beta), subgroup analyses and interim analyses.


[Chronic gastritis--does it need treatment and is it curable?].

FUNDAMENTAL CONSIDERATIONS: Addition to our medical knowledge of chronic gastritis and its sequelae; changes in nomenclature. Presentation of the pathophysiological situation (processes) oft colonization of the gastric mucosa by Helicobacter pylori with particular consideration being given to histomorphological findings. Discussion of the relative risk of gastritis patients contracting a gastric or duodenal ulcer, or possibly developing carcinoma of the stomach. On account of the possible sequela of ulcer and its potential complications, and also the presumably elevated risk of carcinoma, Helicobacter pylori associated chronic gastritis should be submitted to a diagnostic work-up and then treated.


[Gemfibrozil in the differential therapy of disorders of fat metabolism].

In addition to high concentrations of LDL cholesterol, high levels of triglycerides and low concentrations of HDL cholesterol are now known to be independent risk factors in the development of atherosclerosis. The use of Gemfibrozil, with its LDL cholesterol-reducing, HDL cholesterol-raising, and triglyceride-lowering effects, would thus appear to make good sense for the treatment of lipid metabolism anomalies with no selective elevation of LDL cholesterol; it would thus also appear to be superior to HMG-CoA-reductase inhibitors.


[The history of German psychiatry from the viewpoint of French psychiatrists].

The reception of German psychiatry by the French psychiatrists has been influenced by material elements, such as the knowledge of the German language and/or the disposability of translations, but even more by factors of a general nature. The main reason has been the perception by the French psychiatrists of the progressive loss of influence of their own school, initially the leading one in the world, in favour of the German, a change which began with Griesinger and became evident at the time of Kraepelin. Around 1850, as demonstrated by many papers written by leading French psychiatrists, the interest both for the theoretical aspects of German psychiatry and for its care system was great. The judgements were extremely positive, although French authors tended to contrast the philosophical outlook of the Germans with their own concrete clinical approach. The war of 1870-71 produced no radical change. But the growing influence of German psychiatry induced negative reactions whose main target was the work of Kraepelin, and especially his synthesis of Dementia praecox which was in direct opposition with the then dominant concepts of Magnan. The French opinion was divided between defenders and adversaries of Kraepelin's ideas. In the years immediately preceding World War I the attacks increased. The alleged contrast between the descriptive clinical (and according to a German author like Jaspers literary and superficial) French psychiatry and the scientific theoretical (and for the most aggressive French authors valueless) German one was a recurrent theme. The nationalistic tone reached on the French side its apex during the war years, some faint traces remaining several years after 1920. But on the whole the influence of the concepts proposed by German speaking authors, not only Kraepelin, but also Bleuler, Kretschmer, Freud among others was then on the increase. After 1945, contrasting with the years after World War I, no hostility against German psychiatry can be detected, as testified by the choice of the main speakers by the French organizers of the First World Congress of Psychiatry in 1950. The creation in 1984 of the Association of European Psychiatrists, an initiative taken jointly by the French and German psychiatrists, can be considered as the symbolic conclusion of the relations between the two national schools.


[Important asylums in France, Germany and England (1800-1900)].

This study contains a list of the most significant institutions for the care of the insane and also, at a later date, for mentally ill patients. We had to restrict it to the 19th century only and to the areas of Europe where French, German and English are spoken. Many of the most renowned psychiatrists and their publications are classified according to the asylums where they worked. The author refrained on purpose from any analysis or interpretation, glorifying encomiums or accusations, because from the scientific point of view it is more important to place on record the many names, dates and above all the architectural structures of monuments before they get fallen into oblivion.


[Endangerment and dangerousness of psychiatry].

Psychiatry is more influenced by the "Zeitgeist" than other medical disciplines. One important reason is the lack of biological data despite large efforts. In this situation ideological factors may become more relevant than they deserve. Temptations of a "pure" doctrine are dangerous. New developments (methadone substitution, active euthanasia) add to the possible dangerousness of psychiatry. Psychiatrists will have to be careful to avoid this dangerousness and the endangering of their discipline.


[Introduction of shock therapy and psychiatric emigration].

The introduction and general acceptance of shock treatment was intimately connected with the emigration of psychiatrists from the German speaking countries in 1933-1938. In 1934 Manfred Sakel began in Vienna, possibly already in 1933 in Berlin, with insulin shock treatment, and later emigrated to the US. From 1936 Max Müller in Münsingen, Switzerland, practised and propagated the same treatment. Many psychiatric emigrants, on their way to their new countries, visited Münsingen to learn the methods and take them to their future countries of residence (e.g. Lucie Jessner, Gertrude May-Gross, Martin Gross, Ruth Wilmanns, Arthur Kronfeld, Justin Hans Adler and Jacob Peter Frostig). In 1934 Ladislas von Meduna, who emigrated to Chicago in 1939, using campher and Cardiazol also introduced the convulsion treatment. After Cerletti and Bini in Rome had changed the method of provoking convulsions by using electric current, other psychiatric emigrants (Lothar Kalinowsky, Fritz Kant, William Karlinger, Lilly Ottenheimer, Max Rinkel, among others) introduced this method to many countries. In addition, Wagner-Jauregg's best known collaborators for the well-introduced malaria therapy, also had to emigrate. Among these are Helene Deutsch, Josef Gerstmann, Bernhard Dattner and Martha Brünner-Ornstein. The review of life and work of the psychiatrists concerned, before and after emigration, has been complemented by unpublished material.


Utility of the latex agglutination nephelometric immunoassay (Albusure Test) in screening for microalbuminuria in patients with diabetes mellitus.

All diabetic patients should be screened for early signs of diabetic nephropathy, because it is a prognostic factor in the disease. The albusure test (AT), a latex agglutination nephelometric immunoassay, is a rapid and low cost test for the detection of microalbuminuria of 30 mg/L or more. We compared the results of AT and of radioimmunoassay (RIA) for urinary albumin to evaluate the clinical utility of AT using fresh urine samples from 74 diabetic patients without persistent proteinuria and from 11 healthy subjects. Urinary albumin levels were 6.0 +/- 2.3 mg/L in the healthy subjects, 11.0 +/- 8.7 mg/L in the AT-negative group (n = 61), and 38.1 +/- 10.2 mg/L in the AT-positive group (n = 13). Using a cut-off value of 30 mg/L by RIA, the rate of coincidence between AT and RIA was 89.2%, although five subjects were false-positive by AT, and three were false-negative. These results show that AT may provide a useful monitor for microalbuminuria, a reliable early marker of diabetic nephropathy.


[Clinical evaluation of the intraluminal ultrasonography].

Although for the diagnosis of rectal diseases barium-enema and colonoscopy have been commonly carried out, by the methods neither information on the layer structure of the intestinal wall nor swelling of the regional lymphnodes can be provided. Therefore we tried intraluminal ultrasonography (IUS) for further evaluation of the rectum and peri-rectal lesion, and the usefulness of IUS in the rectal disease was described. In 46 cases of rectal cancer, the following results were obtained. Five layer structures were distinguished in the normal rectal wall by the IUS. Intraluminal invasion showed destruction of the layer structures of the colonic wall. The swelling of the regional lymphnodes was revealed as low echoic round mass. In 43 cases with benign diseases, characteristic variations of the layer structures in the colonic wall can be distinguished by the IUS. In conclusion, the IUS was of great use to observe the variation of the layer structure of colonic wall and to provide valuable information on metastasis into the regional lymphnodes.


[A case of obstructive ileus following the upper Gi barium swallow study with condensed barium due to severe constipation].

A 64-year-old woman visited my clinic with complaints of abdominal distension, constipation, and nausea. Since abdominal X-ray showed severe obstructive ileus following the upper GI barium swallow study, the patient was sent immediately to Saga Medical School Hospital for the emergency operation. As the result of the left hemicolectomy, two obstructive lesions were found at the sigmoid colon and the transverse colon. Nowadays, as the population of aged people increases and Japanese diet changes, colon cancers are increasing more rapidly. Since the half of colon cancers doesn't have any clinical symptoms of obstruction, the upper GI barium swallow study with condensed barium might lead a patient to some type of dangerous situation.


[Successful intrauterine digoxin therapy for fetal complete atrioventricular block with endocardial cushion defect: a case report].

We report herein a case of fetal complete atrioventricular block accompanied with endocardial cushion defect, successfully diagnosed and treated, in utero, with transplacental digitalization. A 23-year-old Japanese woman, at 20 weeks of gestation, was referred to the Maternity and Perinatal Care Unit of Kyushu University Hospital because of fetal continuous bradycardia. B-mode scanning and dual M-mode echocardiography revealed that the fetus had complete atrioventricular block with endocardial cushion defect with a ventricular rate of 60 beats per minute. At 23 weeks of gestation, it was found that the fractional shortenings (FSs) in both ventricles and the ventricular rate had decreased, with an increase in pericardial effusion. Thus, we diagnosed the fetus as having cardiac failure. Transplacental digoxin treatment was started and continued for 10 weeks, after which fetal pericardial effusion, as well as FSs ameliorated. The pregnancy was interrupted by cesarean section at 33 weeks of gestation due to a decrease in FSs with an accumulation of fetal ascites. A 1780g female infant was delivered and a pacemaker was implanted surgically, immediately after birth. She is alive and well at the time of writing.


[A case of hyperparathyroid bone disease and the review of renal osteodystrophy].

We report here a typical case of hyperparathyroid bone disease associated with CRF on maintenance HD and review on Renal Osteodystrophy. A 39 year-old female patient was admitted because of polyarthralgia and pruritus. She had a history of HD due to CGN for about 13 years. Laboratory data showed an increase in serum PTH and Alkaline phosphatase level. The evidence of osteitis fibrosa was revealed by bone Xp and scintigraphy. Enlarged solid masses were found in her neck by echogram and parathyroid scintigraphy. She was diagnosed as hyperparathyroid bone disease and total parathyroidectomy c autoplantation was done. Shortly after the surgical treatment, subjective symptoms were relieved and PTH level was normalized. The bone Xp findings improved gradually.


[Senile osteoporosis in normal women examination using dual energy X-ray absorptiometry].

Osteoporosis is now one of the most serious problems in aged Japanese women. We investigated bone mineral contents of the vertebrae of 132 adult women (28-94y.o.) using dual energy X-ray absorptiometry (DEXA) in order to clarify the change of the bone mineral densities (BMD) with aging, and the influences of a diet and exercise on osteoporosis. In the women, BMD of the vertebrae increase to maximum level in 3 rd or 4 th decade of life, and then reduce with aging. The level of BMD is well matched with the index of osteopenia using the lateral view of vertebral X-ray. According as the BMD reduce, the number of bone fractures and the number of patients with bone fractures increase. More than 80% of the women whose BMD are less than 0.7 g/cm2 have bone fractures. In aged women, over 65 year's old, exercise had significant positive effect with BMD, but that was no evidence for influence of calcium intake to BMD.


How blood viscosity influences changes in circulation during pregnancy?

The changes of whole blood viscosity and plasma viscosity were studied in 15 normal non-pregnant women, and 120 normal pregnant women ranging from 8 to 39 weeks of gestation. The values of whole blood viscosity during normal pregnancy were significantly lower from 20 to 31 weeks of gestation than those in the other periods of gestation, and there was a positive correlation between whole blood viscosity and hematocrit. Plasma viscosity, however, did not change significantly during pregnancy. There was no correlation between whole blood viscosity and plasma viscosity, and there was also no correlation between plasma viscosity and plasma fibrinogen concentration. These findings suggest that decreases in whole blood viscosity, resulting from the change of packed-cell volume, may strongly contribute hemorheologically to the decrease in peripheral resistance during the second trimester.


[Effective continuous hemofiltration and plasma exchange for the treatment of subacute type fulminant hepatic failure].

By combination of continuous hemofiltration (CHF) with plasma exchange therapy we successfully treated a patient with subacute type fulminant hepatitis to keep her consciousness alert. The patient was a 55-year-old woman who admitted because of severe jaundice. On the 51st day after the onset she had consciousness disturbance and was transferred to our hospital. We started the therapy of CHF and plasma exchange at the patient's hepatic coma grade 4. On the 5th day her consciousness level recovered to grade 2 and we could keep the level for almost 2 weeks. This combination therapy seemed good not only for the improvement of consciousness of patients in hepatic coma but also to support the hepatic function of almost ahepatic patients.


The history of right heart bypass before Fontan.

Numerous clinical and experimental studies have suggested that adequate pulmonary blood flow and normal central venous pressure may be maintained without significant contribution of right ventricular function. These data induced experimental and clinical research in the quest for complete bypass of the right heart. More than 40 different operations have been designed to bypass the right ventricle. Partial right ventricular bypass was achieved in 1949 by anastomosing the superior vena cava to the pulmonary artery in animal experiments. In 1950 such as operation was successfully performed clinically for the first time. Complete bypass of the right heart was accomplished for the first time experimentally in 1954 by performing a superior vena cava-to-right pulmonary artery anastomosis and implanting the inferior vena cava into the left atrium. Successful clinical bypass of the right heart was carried out later by implanting both vena cavae into the pulmonary circulation. Until the cavopulmonary shunt conclusively proved the validity of the concept that compensated circulation is possible without participation of the right ventricle, surgeons did not fully understand its possible relevance in clinical situations. The development of partial and complete right heart bypass procedures, both experimental and clinical, not only presented us with viable alternatives to aortopulmonary shunts like the Blalock-Taussig or Potts anastomosis, but it also opened the way to development of new operations such as the Fontan procedure which are based on the principle of low pressure pulmonary flow and right ventricular bypass.


Pre-operative assessment of ventricular function in patients considered for Fontan procedure.

In 1978 Choussat and Fontan established ten criteria, which should be fulfilled to achieve a successful outcome in Fontan operation. Recent data suggest that while some of these ten criteria need not be necessarrily be fulfilled, new criteria should be added. These include 1. good diastolic function, 2. normal or only slightly increased ventricular mass, and 3. absence of systemic outflow obstruction. In addition the morphology of the single ventricle may be important as long-term results in patients with single ventricle of right ventricular morphology may be worse than results in patients with single ventricle of left ventricular morphology. Ventricular size and pump function can be assessed by cardiac catherization, echocardiography or magnetic resonance imaging. Estimation of ejection fraction under stress by nuclear angiography may be indicated. Diastolic function can be examined using Doppler echocardiography or nuclear angiography. Myocardial mass may be assessed by echocardiography or magnetic resonance imaging. Normal reference values for different parameters of systolic and diastolic function are listed in the enclosed tables. Patients scheduled for a Fontan operation should have an ejection fraction less than 50%. Patients with borderline ejection fraction should be examined by echocardiography to determine the end-systolic wall stress, a parameter of ventricular contraction, which is independent of pre- and afterload. As afterload may decrease after a Fontan operation some patients with reduced ejection fraction but normal end-systolic wall stress may still be suitable candidates for Fontan operation.(ABSTRACT TRUNCATED AT 250 WORDS)


The relation between ventricular hypertrophy and clinical outcome in patients with double inlet left ventricle after atrial to pulmonary anastomosis.

To clarify differences between pre- and postoperative volumetric and hemodynamic variables from patients with clinically good and poor outcomes after a Fontan procedure, 40 patients with univentricular heart (double inlet left ventricle) (mean age: 5.7 +/- 3.3 years) were studied using the ventricular cineangiography. According to postoperative clinical findings, patients were classified into two groups: 26 patients with good outcomes and 14 patients with poor outcomes (including five with early and two with intermediate deaths) and compared with a control population. Age at surgery, pre-operative cardiac index, wall mass and systolic ejection phase parameters were not different between the two patient groups, however, end-diastolic volume index in poor outcomes was significantly smaller than those with good outcomes (100 +/- 24, 78 +/- 22, 64 +/- 14 ml/m2: good, poor outcomes and controls, respectively, p less than 0.05), and the mass/volume ratio in this group significantly elevated (1.00 +/- 0.18, 1.19 +/- 0.33, 0.97 +/- 0.19 g/ml, p less than 0.05). Postoperatively, both ventricular volume and mass in good outcomes returned toward the normal and the mass/volume ratio remained within normal range (1.07 +/- 0.22). In contrast, the hypertrophied ventricular mass in those patients with poor outcomes did not decrease in parallel with ventricular volume, thus contributing to a further increased ratio (1.48 +/- 0.19). Although there were no significant differences between pre-operative hemodynamic variables among the two groups, the mass/volume ratio in those with poor outcomes was increased pre-operatively and further increased after the Fontan procedure due to rapid and acute reduction of preload.(ABSTRACT TRUNCATED AT 250 WORDS)


Pathophysiological and metabolic manifestations of pulmonary vascular disease in children.

In children with congenital heart disease pulmonary vascular disease can be fatal for a variety of reasons. Even before the classical changes of advanced pulmonary vascular obstructive disease have developed, a marked increase in pulmonary vascular smooth muscle can be fatal due to pulmonary hypertensive crises. After the Fontan procedure, a modest increase in muscularity can jeopardise the outcome since there is no subpulmonary ventricle to support the pulmonary circulation. Following heart transplantation, a slight increase in muscularity can cause failure of the donor right ventricle unless that heart is already hypertrophied as in the domino procedure. In all children with pulmonary hypertension, either persistent pulmonary hypertension of the newborn or secondary to congenital heart disease the pulmonary vasculature fails to remodel normally after birth. Newborn vessels are characterized by the immaturity of the smooth muscle cells and the paucity of connective tissue. In the hypertensive lung smooth muscle differentiation and connective tissue deposition is accelerated. In children with congenital heart disease intimal changes follow. In these children the potential reversibility of disease following intracardiac repair is determined by the type of pathological change present at the time of repair. However, pulmonary hypertensive crises can occur in young children with potentially reversible disease. Operability is not synonymous with the potential reversibility of pathological lesions. Correlations between structural findings at lung biopsy and haemodynamic findings at cardiac catheterization have improved the accuracy with which the natural and unnatural history of pulmonary vascular disease can be predicted, but is still inadequate because we do not understand the functional implications of the changes.(ABSTRACT TRUNCATED AT 250 WORDS)


On the abolishment of the case manager.

Stabilizing clients in the midst of a psychotic episode in the hospital can be a difficult task that requires a multidisciplinary team. The task of helping those persons to live stable lives of decent quality after they leave the hospital is at least as difficult, and much more complex. Thus, it is not surprising that the case management model, which is not multidisciplinary and is available only on weekdays, is inadequate to deliver well-integrated, constantly available services to difficult clients. The effect on clients is that few are receiving adequate rehabilitation, and many are unstable and frequently rehospitalized. The effect on the system is that a large portion of the mental health budget goes to hospital care, frustrating attempts to reallocate dollars to develop comprehensive services in the community.


Recent advances in studies of the molecular basis of endocrine disease.

The molecular basis for a number of endocrine disorders has been determined in the last several years. Mutations have been described at multiple different steps in the pathways of hormone action. There are now examples of mutations in hormones themselves, hormone receptors, second messenger signalling pathways, and the transcription factors that transduce hormone signals. Several common themes emerge even from the relatively small number of mutations that have been described to date. First, the phenotypic variability that characterizes many endocrine diseases is also reflected in genetic heterogeneity. Some clinical phenotypes that were thought previously to represent distinct diseases can now be interpreted as manifestations of different types of mutations within a single gene. Second, the propensity of certain genes to be targets for frequent mutations may be explained in part by gene structure and organization. Third, although many of the mutations reported initially have been associated with severely affected patients, it is likely that mutations with less severe consequences will also be identified. Genetic polymorphisms within the normal population could also cause subtle differences in hormone or receptor activity, thereby constituting part of the basis for variability in hormone levels and activity. Finally, one can predict continued rapid advances in this field with transfer of genetic testing into clinical practice in the near future.


The role of ras proteins in insulin signal transduction.

Ras-proteins are guanine nucleotide binding proteins, which, in the GTP bound state emit a strong mitogenic signal. In the GDP bound state, the protein appears inactive. We have found that stimulation by insulin of cells expressing elevated levels of insulin receptors results in a rapid conversion of Ras-GDP into Ras-GTP. This process is part of the signalling pathway leading to immediate-early gene expression and a mitogenic response. There seems to be no involvement of Ras-GTP formation in the process of insulin stimulated glucose transport. Though the precise mechanism by which Ras is converted to the GTP bound state remains to be established, a tight correlation exists between receptor autophosphorylation and Ras-GTP formation.


Insulin, at physiological concentrations, enhances the polymorphonuclear leukocyte chemotactic properties.

We investigated the influence of insulin on human polymorphonuclear leukocyte (PMN) chemotaxis induced by mediators in a microchamber assay. Insulin increased, with a dose-response relationship, chemotaxis induced by formyl-methionyl-leucyl-phenylalanine, calcium ionophore and phorbol-miristyl acetate (p = 0.0057, p = 0.0001 and p = 0.0215, respectively). The hormone effect was present also at the physiological concentration of 40 microU/ml. Our data show that insulin affects PMN activity in normal subjects and therefore support the hypothesis that insulin deficiency may be responsible for the impaired PMN function observed in diabetic patients in poor metabolic control.


Effect of melatonin on pulsatile release of luteinizing hormone in female lambs.

This study investigated the effect of melatonin treatment of ewe lambs on LH pulsatility in an attempt to examine the mechanism whereby melatonin advances the onset of puberty. Six ewe lambs were given intravaginal melatonin implants at 12.8 weeks of age. Another six lambs received empty implants. All lambs were serially blood sampled every 15 minutes for six hours on several occasions prior to the onset of puberty. One week after implantation LH pulse frequency and mean LH levels were higher in treated lambs than the control lambs (pulse frequency 0.13/h vs 0.03/h; mean LH levels 2.0 +/- 0.2 ng/ml vs 1.3 +/- 0.1 ng/ml; p less than 0.05). Melatonin treatment failed to alter pulse frequency after the initial increase. Puberty was advanced by 3 weeks in the treated group. In the second experiment six lambs received melatonin implants at 13 weeks of age and another six lambs served as control. In this experiment blood samples were taken intensively during the first few weeks after treatment. Results of this study show that mean plasma LH levels and LH pulse frequency were again higher during the first week after implantation. This transient increase in LH release may be part of the mechanism initiating the eventual advancement of puberty although the significance of this increase is questionable. In both experiments the LH response to estradiol injection was monitored at various times after treatment, but no effects of melatonin were found, although the magnitude of the response increased with age.


Differential effect of adrenalectomy on rat liver metallothionein mRNA levels in basal and stress conditions.

Liver metallothionein (MT) mRNA and serum MT levels of adrenalectomized (ADX) and sham-ADX rats in basal and stress (1, 3 or 6 h of restraint) conditions have been measured. Serum MT levels were overall lower in ADX than in sham-ADX rats. Basal liver MT mRNA levels were increased in ADX rats, suggesting that glucocorticoids have an inhibitory role on the regulation of liver MT synthesis. In contrast, liver MT mRNA levels were increased by stress in sham-ADX but not in ADX rats, suggesting a stimulatory role for glucocorticoids. These results suggest that glucocorticoids have a different role in liver MT regulation depending on the physiological situation.


SMS 201-995 and thyroid function in acromegaly: acute, intermediate and long-term effects.

The acute (TRH-stimulation test), intermediate (0-6 days administration), and long-term (0-30 months administration) effects of SMS 201-995 (octreotide) treatment on thyroid function were studied. Subcutaneous injection of 100 micrograms SMS 201-995 one hour before 200 micrograms TRH intravenously reduced serum TSH response area by more than 50% in 8 healthy volunteers. After 3 days of continuous subcutaneous infusion (CSI) of SMS 201-995 in 9 acromegalic patients (100 micrograms/24 h) a slight but significant decrease in serum total triiodothyronine (TT3) and a concomitant increase in serum TSH were demonstrated, indicating an initial inhibitory effect on peripheral deiodination of thyroxine. After a further 3 days treatment serum T3 and TSH had returned to prevalues. Six of the nine acromegalics were treated with SMS 201-995 (100-1500 micrograms/24 h) and admitted for diurnal hormone profiles on 13 occasions over 30 months. Apart from a barely significant increase in serum TSH, no changes in thyroid function were noted. The study was especially designed to detect minute changes over time in thyroid hormones. The only long-term effect of SMS 201-995 was the barely significant clinically irrelevant increase in serum TSH, possibly caused by a slight inhibition of peripheral deiodination of thyroxine.


Comparative effect of clonidine and growth hormone (GH)-releasing hormone on GH secretion in adult patients on chronic glucocorticoid therapy.

Glucocorticoids are thought to inhibit growth hormone (GH) secretion through an enhancement of endogenous somatostatin tone. The aim of our study was to evaluate the effects of GH-releasing hormone (GHRH) and clonidine, an alpha-2-adrenergic agonist which increases GH secretion acting at the hypothalamic level with an unknown mechanism, on GH secretion in seven adult patients (3M, 4F) with non endocrine diseases and on daily immunosuppressive glucocorticoid therapy. Eleven normal subjects (7M, 4F) served as controls. Steroid-treated patients showed a blunted GH response to GHRH (GH peak 8.3 +/- 3 micrograms/L) with respect to normal subjects (GH peak 19.3 +/- 2.4 micrograms/L). The GH responses to clonidine were also blunted (p less than 0.05) in steroid-treated patients (GH peak 5.8 +/- 2.8 micrograms/L) with respect to normal subjects (GH peak 17.6 +/- 2.3 micrograms/L). No significant differences between the GH responses to GHRH and clonidine were observed either in steroid-treated or in normal subjects. Clonidine is not able to enhance GH secretion similar to GHRH in patients chronically treated with steroids. It can be hypothesized that clonidine does not elicit GH secretion decreasing hypothalamic somatostatin tone.


Endocrine disorders in 66 suprasellar and pineal tumors of patients with prepubertal and pubertal ages.

Tumor oncotypes, initial symptoms and endocrine disturbances before and/or 1 month after surgery were studied in 66 patients with prepubertal and pubertal ages having suprasellar or pineal intracranial tumors. Neoplasms found in patients of prepubertal age were: 15 craniopharyngiomas (CRA), 24 neuroepithelial-cell-derived tumors (NEC), 5 germ cell tumors (GERM) and 4 other lesions (OTHER). In patients of pubertal age, there were 7 CRA, 7 pituitary tumors (PIT), 2 NEC, 1 GERM and 1 OTHER. Approximately 90% of patients had visual abnormalities as one of the initial signs and symptoms, while 59% had increased intracranial pressure. Short stature was observed in only 10% of patients. Before surgery, somatotropic function was found to be deficient (by 2 pharmacological tests) in 90-100% of patients with CRA, PIT or GERM and in 40% of patients with NEC. Overt hypothyroidism was found in 5-25% of CRA, NEC or GERM but in 40% of PIT. Abnormal TSH responses to TRH were observed in 64% of CRA and in 29% of NEC. Low basal serum cortisol was found in 21 or 6% of patients with CRA or NEC, but in 100 or 60% of patients with PIT or GERM, respectively. Diabetes insipidus was diagnosed in 13.6% of all patients. Surgery produced few additional disturbances in endocrine function, except for the incidence of diabetes insipidus which was doubled. Gonadotropic deficiency was found in most patients of pubertal age with CRA and PIT. They were readily differentiated by the high prolactin or growth hormone (GH) levels of the latter.(ABSTRACT TRUNCATED AT 250 WORDS)


Growth hormone response to thyrotropin-releasing hormone in acromegalic patients: reproducibility and dose-response study.

The aim of the study was to analyze 14 consecutive patients with active acromegaly who had not undergone any therapy, the dose response of growth hormone (GH) to thyrotropin-releasing hormone (TRH), the existence of reproducibility of such response as well as to rule out the possibility of spontaneous fluctuations of GH which would mimic this response. On several nonconsecutive days, we investigated the GH response to saline serum, 100, 200 (twice) and 400 micrograms of TRH administration. We also studied both basal serum prolactin, serum prolactin after TRH administration and thyrotropin values. Our results show an absence of GH response after saline serum infusion, whereas after TRH doses, 36.3 42.8 and 45.4% positive responses were obtained, respectively. All GH responders were concordant to the different doses administered. The mean of GH concentrations of the different doses at different times did not reach significant differences. The response to the administration of the same dose brought about a significative increase, although it was not identical. It demonstrated a progressive increase of the area under the response curve, as did the means of increments after each TRH administration, albeit without reaching statistical significance. Between the GH-responding and GH-nonresponding groups there were no differences in either basal serum prolactin or serum prolactin and thyroid-stimulating hormone levels after TRH stimulation. The present study clearly shows that TRH elicits serum GH release from GH-secreting pituitary tumors. The response was reproducible in qualitative terms rather than quantitative, and no dose-response relationship was found between the TRH concentrations and the amounts of GH secreted.


Evaluation of GH paradoxical responses to TRH and LHRH in acromegalic patients during long-term treatment with octreotide.

In some acromegalics, GH release can be induced by TRH and/or LHRH administration. The pathogenesis of these GH paradoxical responses was supposed to be a somatotroph-reduced sensitivity to somatostatin, somatotrophin release-inhibiting factor (SRIF), or an hypothalamic derangement of the SRIF release. In this study, this hypothesis was investigated by means of GH suppression during chronic therapy with octreotide [Somatostatin analogue (SMS)] in order to evaluate the possible correlation between GH and insulin-like growth factor 1 (IGF-1) normalization and the disappearance of these paradoxical responses in 15 acromegalic patients: 15/15 with a paradoxical GH rise after TRH and 7/15 with a paradoxical GH rise after LHRH. SMS therapy was administered subcutaneously at the dose of 150-450 micrograms/day. During the treatment, GH and IGF-1 levels normalized in 12 patients and were reduced in the remaining 3 others. The GH response to TRH disappeared in 7 patients, while the GH response to LHRH disappeared in 4 patients. chi 2 analysis failed to show any significant correlation between GH and IGF-1 normalization and the disappearance of GH response to TRH and LHRH (chi 2 = 0.00686). No linear correlation existed between GH/IGF-1 decrease and GH peak or area under the curve at any time ('r' values: TRH test, GH -0.47, IGF-1 -0.48; LHRH test, GH -0.50, IGF-1 -0.49). The absence of any significant correlation between GH/IGF-1 normalization and the disappearance of GH paradoxical responses during chronic octreotide administration suggests that other factors apart from SRIF sensitivity are involved in the genesis of these responses.


Histology of skeletal muscle in adults with GH deficiency: comparison with normal muscle and response to GH treatment.

The histology of needle biopsy specimens of skeletal muscle from the vastus lateralis was quantitatively assessed in a group of adults with growth hormone (GH) deficiency, most of whom had hypopituitarism treated with conventional pituitary hormone replacement. The mean age of the 21 patients (16 males and 5 females) was 39 +/- 2 (SEM). Comparisons were made with age- and sex-matched controls following six months double-blind, placebo-controlled treatment with recombinant human GH (rhGH) in the GH-deficient patients. Before treatment, needle muscle biopsies from patients with GH deficiency showed mean type I and II fibre areas of 5,153 +/- 273 and 4,828 +/- 312 microns 2 respectively, which did not differ from the controls (4,482 +/- 306 and 4,699 +/- 310 microns 2). Percentages of type I fibres were similar in the two groups (47.2 +/- 2.5% in GH deficiency and 45.3 +/- 2.2% in controls). No difference in the variability of type I or II fibre areas was demonstrated between the groups. Correlations between the relative contribution to total fibre area by type I fibres (mean fibre area x percent) and maximal oxygen uptake (p = 0.006), and between type II fibres and quadriceps force (p = 0.035) were noted in GH-deficient adults before treatment. Following rhGH treatment, no change was noted in mean fibre areas, variability of fibre areas, or percentage of either fibre type.(ABSTRACT TRUNCATED AT 250 WORDS)


Serum osteocalcin levels do not change during rapidly induced hypercalcemia in healthy subjects.

Since osteocalcin has been suggested to play a role in calcium homeostasis, we investigated its serum levels in 6 healthy subjects during a rapid calcium infusion. Serum levels of intact parathyroid hormone (PTH), 25-hydroxyvitamin D [25-(OH) D3] and 1,25-dihydroxyvitamin D [1,25-(OH)2 D3] were also determined. The calcium infusion increased plasma-ionized calcium levels from 1.25 +/- 0.04 to 1.54 +/- 0.07 mmol/l at 30 min (p less than 0.05). Concomitantly, serum levels of intact PTH declined from 2.1 +/- 0.9 to 0.2 +/- 0.3 mmol/l (p less than 0.05). In contrast, serum osteocalcin levels did not change. Further, during calcium infusion, serum levels of 1,25-(OH)2 D3 decreased from 81 +/- 17 to 75 +/- 15 pmol/l (p less than 0.05) whereas serum levels of 25-(OH) D3 did not change. The results therefore suggest that calcium per se does not influence osteocalcin secretion.


Mechanisms of vasopressin secretion.

The magnocellular vasopressin system of the rat has been studied intensively in recent years. This review outlines the electrophysiological characteristics of vasopressin neurons, the characteristics of stimulus-secretion coupling in the neural lobe, and describes some of the major features of the neural regulation of this system which underlie physiological regulation of vasopressin release by osmoregulatory stimuli. The major afferent pathways to the magnocellular system are now well characterised. Those involved in osmoregulation have been mapped using expression of the primary response gene c-fos as a marker for neuronal activation.


Effect of growth hormone on liver glycogen accumulation in suckling rats.

The regulation of liver glycogen turnover in the neonatal period differs from that of the adult state. Little is also known about the regulation exerted by GH in the first period of life. To shed light on the regulation of glycogen production and in particular to study the role of GH on liver glycogen accumulation, we investigated the effect of GH administration in control or GH-deficient neonatal rats. A slow-release GH preparation was injected subcutaneously on days 9 and 12 of life, in normal and neonatally treated rats with thyroxine or cortisol. Seventy-two hours after the last GH administration, liver glycogen was increased without concomitant elevation of plasma insulin and corticosterone levels and in addition without sequential inactivation of glycogen synthase. These data strongly suggest that the current concepts on the regulation of the hepatic synthesis of glycogen should be revised.


Smoking effects on the hormonal balance of fertile women.

We evaluated serum pituitary hormones (prolactin, follicle-stimulating hormone, luteinizing hormone), gonadal hormones (estrone, estradiol, progesterone), sex steroid binding protein (SBP) and urine estrogens in 684 healthy fertile women, subdivided into smokers (n = 237) and nonsmokers (n = 447). The aim of the work was to elucidate whether smoking habits can affect hormonal balance. Smoking interference of estrogen metabolism has been postulated, but no unequivocal data have been reported. A protective role against breast cancer has even been suggested on the basis of a reduced estrogenic activity found in smokers. Our data showed a considerable interference of smoking on PRL secretion, probably related to a direct inhibiting activity of nicotine. Estrogen catabolism could also be involved, and a catabolic shift of 16 alpha-hydroxylation in favour of 2 alpha-hydroxylated catabolites, via the hepatic cytochrome P-450 system could be hypothesized.


Adrenal- and ovarian-vein steroids and LH response to GnRH in two patients with virilizing adrenocortical adenoma studied by selective catheterizations.

Two women with androgen-secreting adrenal adenomas were studied by selective adrenal- and ovarian-vein catheterization. Blood samples were collected for determination of testosterone, androstenedione, dehydroepiandrosterone sulfate and cortisol. In a preoperative stimulation test with gonadotropin-releasing hormone, the response of luteinizing hormone was enhanced in both subjects. In catheterization studies, the venous gradients for the hormones were not diagnostic for the source of hyperandrogenism in either of the patients.


Calcinosis and metastatic calcification due to vitamin D intoxication. A case report and review.

Vitamin D, a fat-soluble vitamin, can be associated with significant morbidity when prescribed in large doses. We describe a hypoparathyroid patient with vitamin D intoxication who developed painful periarticular calcinosis, nephrocalcinosis with hypertension and chronic renal failure in addition to band keratopathy and hearing loss. He was treated with combination therapy including prednisone, phosphate-binding antacid, phenytoin and disodium etidronate. After 20 months of follow-up there was a significant reduction of periarticular calcinosis, but no improvement in renal function, band keratopathy or hearing loss and possible calcification of the ossicles. The clinicopathologic features of metastatic calcification and the various treatment modalities are reviewed.


Autoimmune insulin syndrome in a patient with progressive systemic sclerosis receiving penicillamine.

The case of a patient with progressive systemic sclerosis, who developed hypoglycaemia and insulin autoantibodies, is described. Repeated blood glucose measurements showed levels less than 2.8 mmol/l. High immunoreactive insulin levels, with undetectable free insulin, led to the discovery of anti-insulin antibodies in the patient's serum. He had no history of exogenous insulin use and was receiving penicillamine treatment. A double mechanism for the autoimmune insulin syndrome in this case is proposed: acting in a patient with increased humoral immunoresponsiveness, penicillamine might have induced the development of insulin autoantibodies.


Ethanol-induced vasoconstriction causes focal hepatocellular injury in the isolated perfused rat liver.

The role of microcirculation in the pathogenesis of alcoholic liver injury was investigated in isolated perfused livers from fed rats. Infusion of ethanol into the portal vein at concentrations ranging from 25 to 200 mmol/L increased portal pressure, which is an indicator of hepatic vasoconstriction, in a concentration-dependent fashion. Portal pressure started to rise immediately on initiation of ethanol load and remained at higher than basal levels throughout the period of ethanol infusion. Release of lactate dehydrogenase, an indicator of cell injury, into the effluent perfusate began to increase after 20 to 30 min of ethanol infusion and continued to increase until the end of the experiment (60 min after the initiation of ethanol infusion). The lactate dehydrogenase level in the effluent perfusate at 60 min was dependent on the ethanol concentration (0 mmol/L, 8 +/- 3 IU/L; 25 mmol/L, 22 +/- 3 IU/L; 50 mmol/L, 51 +/- 11 IU/L; 100 mmol/L, 60 +/- 7 IU/L; 200 mmol/L, 120 +/- 7 IU/L). Simultaneous infusion of sodium nitroprusside (100 mumol/L), a known vasodilator, inhibited significantly the ethanol-induced increases in portal pressure and lactate dehydrogenase release by abolishing hepatic vasoconstriction. In histological examinations focal hepatocellular necrosis, evidenced by trypan blue staining of cell nuclei, was detected predominantly in midzonal and pericentral areas of the liver lobule after 60 min of ethanol infusion. Change in portal pressure during 60 min of ethanol infusion correlated significantly with levels of lactate dehydrogenase after ethanol infusion (r = 0.82; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Vitamin E dietary supplementation protects against carbon tetrachloride-induced chronic liver damage and cirrhosis.

Previous studies have shown that alpha-tocopherol (vitamin E) pretreatment of experimental animals can protect against acute liver necrosis induced by carbon tetrachloride. In this study we investigated whether the increase of vitamin E liver content by dietary supplementation influences chronic liver damage and cirrhosis induced by carbon tetrachloride in the rat. Our data indicate that vitamin E supplementation did not interfere with the growth rate of the animals and increased about threefold the liver's content of the vitamin. Vitamin E supplementation significantly reduced oxidative liver damage, but it was not effective in protecting against development of fatty liver and did not interfere with metabolic activation of carbon tetrachloride. Moreover, vitamin E-fed animals showed incomplete but significant prevention of liver necrosis and cirrhosis induced by carbon tetrachloride. This has been shown by means of histological examination, analysis of serum parameters and biochemical evaluation of collagen content. These results show that an increased liver content of vitamin E can afford a significant degree of protection against carbon tetrachloride-induced chronic liver damage and cirrhosis.


S-adenosylmethionine treatment prevents carbon tetrachloride-induced S-adenosylmethionine synthetase inactivation and attenuates liver injury.

Administration of carbon tetrachloride to rats resulted in induction of hepatic fibrosis and a 60% reduction of hepatic S-adenosylmethionine synthetase activity without producing any significant modification of hepatic levels of S-adenosylmethionine synthetase messenger RNA. The reduction of S-adenosylmethionine synthetase activity was corrected by treatment with S-adenosylmethionine (3 mg/kg/day, intramuscularly). Administration of carbon tetrachloride also produced a 45% depletion of liver glutathione (reduced form) that was corrected by S-adenosylmethionine treatment. After the rats received carbon tetrachloride, a 2.3-fold increase in liver collagen was observed; prolyl hydroxylase activity was 2.5 times greater than that seen in controls. These increases were attenuated in animals treated with carbon tetrachloride and S-adenosylmethionine. The attenuation by S-adenosylmethionine treatment of the fibrogenic effect of carbon tetrachloride was associated with a decrease in the number of rats in which cirrhosis developed.


Papaverine inhibits transcytotic vesicle transport and lipid excretion into bile in isolated perfused rat liver.

Papaverine is a nonspecific smooth muscle relaxant and a phosphodiesterase inhibitor. Its effects on biliary excretion of lipids and horseradish peroxidase were investigated in a single-pass isolated perfused rat liver model. A constant infusion of papaverine (1.6 mumol/min; 40 mumol/L) significantly increased bile flow (microliters per minute per gram of liver) before (2.03 +/- 0.09 vs. 1.0 +/- 0.06) and after sodium taurocholate infusion (2.77 +/- 0.10 vs. 1.88 +/- 0.11). However, papaverine significantly and reversibly reduced biliary excretion of phospholipids and cholesterol (nanomoles per minute per gram of liver) after a 1.0 mumol/min sodium taurocholate infusion, from 7.45 +/- 0.83 and 1.42 +/- 0.15 to 1.75 +/- 0.18 and 0.39 +/- 0.06, respectively (p less than 0.01), whereas secretion of bile acids was unaffected. When a 1-min pulse of horseradish peroxidase (25 mg) was infused in isolated perfused rat liver after a continuous infusion of N6,O-2'-dibutyryladenosine 3',5'-cyclic monophosphate (0.25 mumol/min; 6.25 mumol/L), horseradish peroxidase appeared in bile in an early (4 to 6 min) and late (20 to 25 min) peak. Papaverine significantly reduced the late peak, from 1.211 +/- 0.264 to 0.498 +/- 0.107 (p less than 0.01). Papaverine had no significant effects on either cyclic AMP or cyclic GMP in the liver and bile, although it has been reported that papaverine is a phosphodiesterase inhibitor. These findings indicate that papaverine inhibits biliary excretion of lipids but not bile acids, and they suggest that papaverine has an inhibitory effect on transcytotic vesicle transport independent of an increase of cyclic nucleotides in hepatocytes.