Epidemic hecatomb in the New World.

The American population developed, during thousands of years, free of epidemics that had been attacking Europe, Asia and Africa. The European and African migrations, after Columbus's first trip, produced an epidemic invasion of influenza, smallpox, measles, yellow fever, malaria, diphtheria, typhus, and other diseases that attacked the immunologically virgin populations and produced a very high mortality, with a diminution of the indigenous population of more than 90% in many places. According to historical evidence, the first epidemic was influenza, produced by swine strain of virus, immediately followed by smallpox. The Spaniards mated freely with the Indians producing a mixed race called the Mestizo, who were immunologically more capable of defending themselves against various viruses, bacteria, and parasites brought over from the Old World. Marriage between the races also was sanctioned by Queen Isabella (1503) and Fernando I (1515). With these new genetic immunologic defenses against infections, the Mestizo eventually made up the majority of the population of Indians in the New World.


Genetic difference between Europeans and Indians: tissue and blood types.

When Columbus reached America, the continent probably was inhabited by 15 to 30 million natives. Mexico now has 68 different Indian tribes classified from a linguistic point of view; 5 million people speaking different languages are registered. However, the Mexican population is mainly composed of Mestizos (95%), who have a triracial admixture of Caucasian genes coming from the Spanish conquerors, black genes from the African slaves brought by the Spaniards to America, and an Oriental gene-pool derived from the natives. The admixture started around 1500, but at present it may be very difficult to distinguish phenotypically one group from another, and the Mestizos from the Indians. Therefore, polymorphic systems like the major histocompatibility complex (MHC) or several blood markers are very valuable tools and crucial elements to trace human migrations, to define degree of admixture, and to explore the impact of genetics on the epidemiology of the different populations. The distribution of blood group systems throughout western Europe is very homogeneous. In contrast, in the Mongolian the A2 subgroup and the S allele almost disappear compared with European Caucasian. Although homogeneity also exists in Orientals, several groups have a very particular pattern, such as the Senoi from Malay, the Tharons from Burma and the Ainu from Japan. We analyzed four Mexican Indian tribes, and as in Amerindians group 0 is extremely high, almost all are kappa; Fya is increased as in Mongolians, and Dia is an Oriental and Amerindian marker. The distribution of Lu and Kp suggests that the environment might have influenced the variability of these antigens found in Indians.(ABSTRACT TRUNCATED AT 250 WORDS)


Allergy to pistachio nuts.

Three patients with adverse food reactions due to pistachio and mango were studied. Specific IgE against these tropical stone fruits of the Anacardiaceae family could be demonstrated, indicating type I allergic reactions. Methods are described to detect these specific antibodies in a reproducible way.


Peroxyl radical scavenging by a series of coumarins.

Sixteen plant-derived or synthetic coumarins with various hydroxyl and other substitutions were tested for their ability to scavenge alkylperoxyl radicals generated in the aqueous phase by the controlled thermolysis of 2,2'-azo-bis-(2-amidinopropane) dihydrochloride (ABAP). Protection by coumarins against inactivation of lysozyme by the radicals was assayed by measuring the loss of turbidity of suspensions of M. lysodeikticus. Ten of the coumarins were potent scavengers of aqueous peroxyl radicals with activities comparable to n-propyl gallate, desferrioxamine, ferrioxamine and trolox c, yielding IC50 values in the range 21 to 92 micromolar. The presence of 6,7-ortho-dihydroxy functions gave compounds of the greatest potency. Scavenging activity was unrelated to ability to chelate iron ions. The active coumarins are attractive candidates for evaluation as protective agents against disorders in which oxidative stress is implicated.


Prevalence of dust-mite allergens in homes and workplaces of the Upper Connecticut River Valley of New England.

This study sought to determine the relative abundance and seasonal variation of Dermatophagoides farinae and D pteronyssinus allergens in homes and workplaces of the Upper Connecticut River Valley of New England. Dust samples were obtained from 15 homes and 23 carpeted workplaces in public buildings. Half the samples were collected in June 1990 and half in September 1990. D pteronyssinus and D farinae content of the samples were determined by enzyme-linked immunosorbent assay (ELISA). This observational study of homes and workplaces found a predominance of D pteronyssinus allergens in both homes and workplaces; a marked seasonal increase in total Dermatophagoides group I allergens from June to September; and only very low levels of allergens in workplaces. Workplaces seem an unlikely source of significant dust-mite allergen exposure, and workplace exposure does not negate efforts at home dust control by affected patients in this region.


Luminol luminescence induced by 2,2'-Azo-bis(2-amidinopropane) thermolysis.

2,2'-Azo-bis(2-amidinopropane) thermolysis induces luminol luminescence. The luminescence intensity is quenched by SOD, catalase, Trolox and human blood serum. However, the time course of the light intensity profile is different for the different additives. In particular, the quenching efficiency of Trolox and human blood serum decreases with time after addition. Double quenching experiments show that SOD and Trolox are not competitive quenchers, while a simple competition can be established between Trolox and human blood serum in trapping a common intermediate. From the kinetic analysis of the data it is concluded that, at least at low additive concentrations, Trolox scavenges a luminol derived radical. Higher concentrations of Trolox or human blood serum produce induction times that are proportional to the additives concentrations. The possibility of employing luminol luminescence in the evaluation of TRAP levels and the capacity of biological samples to scavenge free radicals is discussed.


Oxygen-derived free radicals mediate liver damage in rats subjected to tourniquet shock.

The placement of rubber band tourniquets upon rat hind-limbs for 5 h followed by reperfusion of the extremities results in a severe form of circulatory shock characterized by hypotension and death within 24 h of tourniquet release. Oxidative damage to muscle tissue is an early consequence of hind-limb reperfusion on tourniquet release, yet this local damage does not explain the lethal hypotensive shock state which evolves within the next 24 h. Multiple system organ failure (MSOF), of as of yet unknown causes, is usually described in relation to several shock states. It has been suggested that injured or necrotic tissue may activate neutrophils, platelets, and the coagulation system leading to embolization in remote tissues. Effective decreases in hepatic blood flow have been observed in several forms of sepsis which precedes the biochemical evidence consistent with an ischemic insult of the liver. In support of our original hypothesis, that organ failure has its genesis in a primary perfusion abnormality with secondary ischemic organ injury, herein we have assessed the possibility that oxygen-derived free radicals are generated in the liver of rats after reperfusion of their hind-limbs on release of the tourniquets. We report on the protective effects of allopurinol (ALLO) and a mixture of superoxide dismutase (SOD) catalase (CAT) and dimethylsulfoxide (DMSO) on liver free sulfhydryl content (SH), thiobarbituric acid-reactive substances (TBARS), and on the release of aspartic acid (AsT) and alanine aminotransferase (AlT) activities, and of alkaline phosphatase during a 5 h tourniquet period and after 2 h of reperfusion of the hind-limbs. During the hind-limb ischemic period hepatis tissue SH levels remained essentially constant during the first hour (6.02 +/- 0.36 to 5.65 +/- 0.20 mumoles/g wet tissue), and decreased significantly, over and above the normal circadian decrease of liver glutathione levels, to 4.02 +/- 0.69 mumoles/g wet tissue after the third hour and remained lowered until tourniquet release. A further significant decrease (3.11 +/- 0.49 mumoles/g wet tissue) was observed after 2h of reperfusion. TBARS production remained constant during the 5 h hind-limb ischemic period (168.4 +/- 37.3 mumoles/g wet tissue) and rose by 55% to 261.7 +/- 55.8 mumoles/g wet tissue after 2 h of tourniquet release. ALLO, but not the SOD-CAT-DMSO combination, protected hepatic SH loss during the hind-limb ischemic insult, yet both offered protection after 2 h of tourniquet release.(ABSTRACT TRUNCATED AT 400 WORDS)


Effect of ozone on the activities of reactive oxygen scavenging enzymes in RBC of ozone exposed Japanese charr (Salvelinus leucomaenis).

The effect of ozone exposure on the activities of reactive oxygen scavenging enzymes (SOD, catalase, GSH-Px) in RBC of Japanese charr (Salvelinus leucomaenis) was examined. Ozone (0, 0.4 and 0.7 ppm as initial concentrations) was exposed to Japanese charr for 30 min, which definitely caused serious membrane damage to RBC of fish. Ozone exposure at 0.4 and 0.7 ppm decreased activities of both catalase and GSH-Px by 80 to 57% of the control. On the other hand, the activities of SOD remained unaffected even by 0.7 ppm ozone exposure. A hypothesis on the RBC membrane damage and participation of SOD and heme-iron was proposed.


Magnitude of hyperoxic stress and degree of lung maturity determine the nature of pulmonary antioxidant response in the guinea pig.

The ability of the immature lung to induce antioxidant defences in response to hyperoxic stress was examined. Preterm guinea pigs (65 days gestation, term = 68 d) were exposed to either 21% O2, 85% O2 or 95% O2 for 72 hours. Exposure to 85% O2 increased lung catalase, glutathione peroxidase and manganese superoxide dismutase activities in comparison to air controls. Exposure to 95% O2 resulted only in an increase in glutathione peroxidase activity. Bronchoalveolar lavage fluid GSH concentration was increased by a similar amount by both exposure regimes, while lung copper/zinc superoxide dismutase activity was unchanged by either treatment. Comparison of the antioxidant response of term and preterm animals exposed to 85% O2 for 72 hours indicated a greater response in the lung of the preterm animals. Manganese superoxide dismutase activity was elevated in both term and preterm animals, while catalase and glutathione peroxidase activities were elevated only in preterm animals. The extent of microvascular permeability as indicated by bronchoalveolar lavage fluid protein concentration, was lower in preterm animals than in term animals. We conclude that the immature lung can respond to hyperoxic stress by antioxidant induction and that the nature of the response is dependent, in part, both on the severity of the stress and on the maturity of the lung.


Chronic rhinitis: an underrecognized association with fibromyalgia.

We prospectively studied 47 consecutive patients with either seasonal or perennial allergic rhinitis or nonallergic rhinitis in a general allergy clinic. A diagnostic questionnaire was administered for symptoms of rhinitis and fibromyalgia, and patients were examined for tender points. A history of congestion was present in 91%, rhinorrhea in 87%, and postnasal drip in 83%. Forty-nine percent had a history of diffuse, aching pain, or tiredness for at least 3 months; 49% percent had 11 or more tender points; and 38% had both a history of widespread pain plus 11 or more tender points (the 1990 criteria of the American College of Rheumatology for fibromyalgia). This frequency is much higher than the expected 4 to 5% prevalence of fibromyalgia in a general population. Seventy-nine percent of all subjects were skin-test positive to inhalant allergens, but positive skin tests alone did not correlate with the number of tender points or criteria for fibromyalgia. Rhinitis, rather than atopy, is associated with fibromyalgia and may be an underdiagnosed, but important causative factor.


Paraneoplastic marrow alterations in patients with cancer.

Bone marrow abnormalities may be found in patients with cancers even without marrow metastases. We have seen that patients with non-hematologic neoplasias may show bone remodelling, stromal modifications, reactive changes and myelodysplastic alterations of erythro-, granulo- and megakaryocytic series comparable to those found in myelodysplastic syndromes (MDSs). At the beginning of the study 58 bone marrow biopsies (BMBs), performed in 40 patients with previously diagnosed cancer from different primary sites but without marrow metastasis (group A), were evaluated. Osseous and stromal modifications, marked reactive changes, quantitative and qualitative alterations of erythro-, granulo- and megakaryopoiesis were observed. Afterwards, 30 BMBs from 20 patients without a previous diagnosis of neoplasia (group B) were found to have features similar to those discovered in group A. Further investigations detected malignant tumors in all these cases. The findings of the two groups were compared with our former observations on myelodysplastic syndromes. The main differences between groups A-B and MDSs regarded bone remodelling, stromal modifications and reactive changes. These marrow alterations linked to a neoplasia may be considered paraneoplastic. They may cause problems for a differential diagnosis with some proliferative diseases and, above all, with primary MDSs. The reported features should prompt the pathologist to suggest a search for possible occult cancer.


Primary gastric non-Hodgkin's lymphoma in a population-based registry.

The incidence of primary gastric non-Hodgkin's lymphoma (NHL) appears to have increased worldwide in recent years, and this seems to be confirmed by large-sample population studies. We derived our data from the Lombardy Cancer Registry, which provides the incidence of cancer in the province of Varese, Northern Italy. From 1978 to 1987 we identified 3261 cases of gastric neoplasms, 119 of which were gastric NHL: 32 (1.87%) from 1978 to 1982, and 87 (5.32%) from 1983 to 1987. The difference in the age and sex standardized incidence trend between these two time periods was statistically significant (p < 0.001). The overall survival rate of the 112 evaluable patients was 54% at 5 years and 45% at 10 years. A multivariate analysis was performed. Age (p < 0.0005), clinical stage (p < 0.04) and therapy (p < 0.0005) were found to be significant prognostic factors for survival. This study stresses the utility of prospective randomized clinical trials that could indicate the optimal management of patients with primary gastric lymphoma.


HIV-related thrombocytopenia: four different clinical subsets.

Many factors have been considered in the pathogenesis of HIV-related Thrombocytopenia (HIV-rel TP): immunological destruction, retroviral infection of megakaryocytes and altered reticulo-endothelial function. Nevertheless the pathogenesis is still controversial. We reviewed 52 patients (all intravenous drug users) with HIV-rel TP (< 100 x 10(9)/L) by evaluating bone marrow morphology, antiplatelet antibodies (28/52), kinetic studies with 111In Oxine and response to therapy. Seventeen percent of TP were evaluated as "acute ITP-like", and 40% as "chronic ITP-like"; 35% were evaluated as "pooling" TP and 8% as "hypoplastic" TP. Twenty-four patient with moderate TP (> 30 x 10(9)/L) were followed for a mean time of 27 months and no hemorrhages were seen during the period of observation despite the fact that no treatment was given; twenty-eight others with severe TP (< 30 x 10(9)/L) were treated in different ways: 18% responded to steroids and/or HDIg, 70% to splenectomy and 56% to zidovudine. The term "HIV-related thrombocytopenia" should include more than one kind of TP: "Acute ITP-like" TP, "chronic ITP-like" TP, "pooling" TP and "hypoplastic" TP have to be evaluated differently for pathogenesis, clinical manifestations and treatment.


Sex and age as prognostic factors in essential thrombocythemia.

The major causes of morbidity and mortality in essential thrombocythemia (ET) are bleeding and thrombotic accidents, but a prognostic pattern for these complications has not yet been discovered. In this study we report data from a large cohort of patients with thrombocytosis, distinguished for sex and age, in order to define their thrombotic risk. The prevalence of vascular complications recognized in 86 patients with essential thrombocythemia was studied. In addition, 91 patients with polycythemia vera (PV), 20 with myelofibrosis (MF) and 63 with secondary thrombocytosis (ST) were evaluated. 6.3% of ET subjects younger than 40 (4.6% of males and 7.0% of females), 11.8% of patients between 40 and 65 years old (14.9% of males and 9% of females), and 16.8% of subjects over 65 (14.6% of males and 17.8% of females) showed thrombotic accidents. In the PV and MF groups thromboses occurred more frequently than in the ET groups for all ages and for both sexes. On the contrary, ST subjects showed fewer thromboses than ET patients, but their incidence rose with patient age; moreover the prevalence of males in this group was limited. In ET patients, particularly in females, the incidence of thrombosis was low under 40 years of age, but rapidly increased later. ET females over 40 must be followed with particular attention in order to prevent thrombotic complications.


[The role of neuronal cytoskeleton associated proteins in neuronal network formation].

There have been many studies to determine extrinsic factors that may regulate the neuronal migration and growth of axons and dendrites. However, the intracellular mechanism, especially the regulation of cytoskeleton, has not been clarified. It has been reported that actin filament crosslinking protein, MAR-CKS, play roles in cell motility through cytoskeletal rearrangement accompanied by rapid, PKC-dependent phosphorylation. Recently, we have demonstrated that neuron-specific actin binding protein, drebrin, changed the stability and distribution of microfilaments within the fibroblast and formed highly-branched dendrite-like cell processes from their cell perimeters. It has also been reported that overexpression of microtubule associated protein, tau, in a fibroblast induced long axon-like cellular processes. This review will focus on dynamic regulations of the microfilament by drebrin and those of the microtubules by MAP2 and tau. Since all kinds of cytoskeletons are related to each other, the binding ability of neurofilament H to microtubules and that of MAP2 to neurofilaments were also discussed.


Low-dose "natural" alpha-interferon in B-cell derived chronic lymphocytic leukemia.

Alpha-interferon (alpha-IFN) was found to have a good antiproliferative effect in early stage chronic lymphocytic leukemia (CLL), but recombinant alpha-IFN administration may induce serious side effects. Therefore low-dose "natural" IFN was evaluated in terms of efficacy and safety. Fifteen patients affected by stage A (according to Binet) B-CLL underwent the treatment: natural IFN 1 MU three times a week for 6 months. Overall lymphocyte count decreased from 13,050 +/- 3,200 to 7,500 +/- 2,940 within 6 months. One patient did not respond to IFN therapy. No one complained of side effects. Low dose "natural" alpha-IFN seems useful and well tolerated in CLL, but the potential curative role of IFN in CLL remains to be established.


Idiopathic hypereosinophilic syndrome and "eosinophilic leukemia".

We report a case of idiopathic hypereosinophilia syndrome (H.E.S.) with a pronounced myeloproliferative disorder, which during the course of the illness has exceeded more than one "blastic crisis". This again proposes the difficult relationship between H.E.S. and myeloproliferative syndromes (M.S.), and is indicative of why some cases of H.E.S. are differentially diagnosed as chronic myeloid leukemia (C.M.L.) with an eosinophilic component.


[Establishment of a method to analyze drugs in the hair and its application for determining patient compliance].

The human scalp hair is a useful tissue that retains the past dosage history over a rather long period of time, acting like a "tape-recorder". It should be emphasized that the sampling of hair can be made noninvasively by cutting a few to several pieces of hair nearest to the scalp. Because the hair continues to grow at the rate of about 1 cm/month, each 1-cm hair length contains the drug corresponding to the amount ingested over a 1-month period when the hair is cut into 1-cm lengths successively from the scalp end. However, the hair growth rate is variable both within and between individuals, and the hair has its own growth cycle, i.e., 2 to 8 years or more of the growing stage and a few months of the resting stage. Therefore, the validity of the obtained results must always be considered cautiously, especially in relation to whether a resting phase hair might have been sampled. For obtaining information on the growth rate and stage of a hair, a drug that can be detected in the hair even after a short-term exposure to the drug has been found. These drugs are antimicrobial quinolones such as ofloxacin. By analyzing the axial distribution of ofloxacin along the hair shaft, we can expect to determine the so-called "tape-speed" and "uniformity of tape-running" of a single hair.


Biochemical and molecular basis of Glanzmann's thrombasthenia.

Glanzmann's thrombasthenia is a rare autosomal recessive bleeding disorder characterized by a quantitative deficiency or a functional abnormality of the major platelet membrane integrin receptor: the glycoprotein (GP) IIb/IIIa complex. The GPIIb/IIIa complex functions as a platelet receptor for fibrinogen, von Willebrand factor, fibronectin and vitronectin; therefore it plays an important role in platelet adhesion and aggregation. Thrombasthenic platelets are severely deficient in GPIIb/IIIa content or function, and fail to aggregate and form the hemostatic plug at the site of vessel injury. On the other hand, heterozygous subjects (having about half the number of normal GPIIb/IIIa complexes) do not show bleeding problems. It has been demonstrated that a molecular defect affecting one of the two GP coding genes is sufficient to determine a contemporary deficit of both GPIIb and GPIIIa, and hence the thrombasthenic phenotype. Up to now, few molecular abnormalities giving rise to Glanzmann's thrombasthenia have been characterized. Large rearrangements within the GPIIb or GPIIIa coding genes appear to be unusual, whereas small modifications in the nucleotide sequence of the coding regions occur with higher frequency.


Interferon therapy in intravenous drug users with HIV-associated idiopathic thrombocytopenic purpura.

There is no generally accepted treatment for human immunodeficiency virus (HIV)--associated idiopathic thrombocytopenic purpura (ITP). recombinant alpha interferon (rIFN) has been used in classic ITP with conflicting results. We have tested its activity in a group of intravenous drug users (IVDUs) with HIV-associated ITP, who also had a high prevalence of chronic liver disease. Nine patients were treated with a short course of rIFN-2b (3 MU s.c. three times a week for four weeks), and their hematological and biochemical parameters were monitored before (t0), at the end (t1), and one month after discontinuation of rIFN therapy (t2). Platelet counts increased significantly from 15.9 +/- 7.3 x 10(9)/L at t0 up to 67.0 +/- 38.8 x 10S(9)/L at t1 (p < 0.005), but returned to 24.7 +/- 12.7 x 10(9)/L at t2 (t1 vs t2: p < 0.005). The other parameters did not change, with the exception of the alanine aminotransferase levels, which decreased from 105 IU/L at t0 to 42 IU/L at t1 (p < 0.05). A short course of rIFN is an effective treatment for HIV-associated ITP in IVDUs and may also be beneficial for the frequently concomitant chronic liver disease. Since the efficacy of rIFN on the platelet count is short-lived, long-term rIFN administration would be worth testing.


"Very late" relapses in Hodgkin's disease patients: a rare but real phenomenon.

In the past several decades, scientific and therapeutic advances have transformed Hodgkin's disease from a uniformly fatal illness to one that can be treated with the expectation of long-term remission or cure in the majority of cases. Because patients now survive for long periods after treatment, various late complications are being identified. Among patients with such late complications, some have been reported to experience "very late" relapses (> 10 years). Here we document recurrences in three patients with Hodgkin's disease more than 10 years after remission.


Kinematics of the ankle: a hinge axis model.

We used a mechanical method to locate the axis of rotation of the talocrural joint. A single constant axis of rotation was found just distal to the tips of the malleoli. The paths of light-emitting diodes mounted on a talar pin were recorded with time lapse photography during flexion-extension. These paths were analyzed both in the sagittal plane and in a plane perpendicular to the axis of rotation. Sagittal plane studies were distorted by perspective error. The plane used to analyze joint motion or shape must be the plane of motion. Models of the talocrural joint for gait analysis, reconstructive surgery and prosthetic design should have a single offset axis of rotation.


Polycythaemia after myeloid metaplasia with fibrosis: an unusual sequence.

In November 1981, a 77-yr-old woman consulted for myeloid metaplasia with fibrosis. A persistent hyperleucocytosis was treated with hydroxyurea from March, 1985 to March, 1989. At that time facial dyskinesia and polycythaemia developed. Investigations revealed a regression of myelofibrosis and a predominance of myeloid metaplasia in the liver. The mechanism of this event, rarely observed in myeloproliferative syndromes, is discussed in this new case.


Treatment of hallux valgus by oblique osteotomy of the first metatarsal.

This paper describes a simple technique of oblique osteotomy of the first metatarsal for treatment of symptomatic hallux valgus deformity. The osteotomy is performed at a 30 degree angle from the long axis of the metatarsal shaft. The head of the metatarsal is then displaced laterally to provide correction of the hallux valgus. This is an uncomplicated procedure for the treatment of hallux valgus. From 1984 through 1989, 53 feet in 31 patients were treated with an oblique osteotomy of the first metatarsal. A total of 49 feet in 27 patients were followed up more than 2 years. The follow-up x-rays and clinical examinations revealed a good result in 43 feet. In six feet of three patients, all of whom had simultaneous oblique osteotomies of both the first and second metatarsals, a fair or poor result was obtained. It was learned that oblique osteotomy for hallux valgus greater than 40 degrees provided insufficient correction of the valgus angle or limitation of motion at the metatarsophalangeal joint of the great toe.


Acute lymphoblastic leukaemia in a child with cystic fibrosis.

The association of cystic fibrosis (CF) and acute lymphoblastic leukaemia (ALL) is extremely rare. Only three cases have been reported in the literature and all of them had a fatal outcome. In this paper we describe the case of a little girl who was diagnosed with CF (mild course) when she was five months old, and who presented at the age of five years with ALL (intermediate risk). Complete Remission (CR) was rapidly obtained with standard chemotherapy for ALL.; treatment was continued for two years without major complications and with no apparent influence on the course of CF. The patient remains alive and well and in continuous CR four years after discontinuing treatment, and six years after the diagnosis of ALL.


Excision of ununited fractures of the posterior process of the talus: a treatment for chronic posterior ankle pain.

The cases of nine patients with ununited fracture of the posterior process of the talus were reviewed. The most common mechanism of injury was forced plantarflexion. All patients had pain in the posterior ankle region. Common physical findings included tenderness between the lateral malleolus and the Achilles tendon and pain on forced plantarflexion. Of the radiographic imaging modalities used, 99Tc bone scan was found to be the most helpful in diagnosis. All nine patients eventually underwent surgical excision at a mean period of 9.4 months post injury. At average follow-up of 27 months after surgery (range 7-69 months), six of nine patients had good or excellent results with respect to pain relief and return to function. There were two complications of sural neuroma formation, one of which resulted in severe persistent pain after surgery. Based on these findings, we believe the differential diagnosis of chronic posttraumatic ankle pain should include fracture of the posterior process of the talus. Furthermore, excision of an ununited fragment through a lateral approach, taking care to preserve and protect the sural nerve, should lead to the return of painless function in the majority of cases.


Anatomical considerations of posterior tibialis tendon entrapment in irreducible lateral subtalar dislocation.

Irreducible lateral subtalar dislocation is associated with posterior tibialis tendon entrapment. Mulroy and Leitner have proposed conflicting theories regarding the exact mechanism of tendon entrapment. Cadaveric analysis of lateral subtalar dislocation supported Leitner's contention that tearing of the flexor retinaculum promotes posterior tibialis tendon entrapment. Retinacular disruption allowed tendon subluxation over the medial malleolus and talar head to the entrapped position. Entrapment of the flexor digitorum longus only occurred in the Leitner model. When the flexor retinaculum and deep posterior compartment fascia were preserved, the muscle failed at the musculotendinous junction. Flexor hallucis longus entrapment could not be produced in either experimental model. Plantarflexion of the great and lesser toes, noted on clinical presentation, is caused by functional lengthening of the route coursed by the flexor digitorum longus and flexor hallucis longus.


The Harris and Beath footprint: interpretation and clinical value.

The Harris and Beath footprint is an inexpensive, noninvasive method of recording foot/ground pressure patterns to aid clinical diagnosis, decision making, and follow-up. Studies of normal children and skeletally mature individuals have identified the wide variations found in normal feet, a knowledge of which is fundamental to the interpretation of the footprint in the clinical situation.


Microvascular anatomy of the peroneal tendons.

The etiology of longitudinal splitting of the peroneus brevis tendon is unclear. It has been hypothesized that compressive load applied to the tendon as it passes through the fibular groove may compromise the vascularity of the tendon with resultant inhibition of the repair response and degeneration of tendon structure. To investigate this possibility, a study of the microvascularity of the peroneal tendons was undertaken. Twelve fresh, frozen cadaveric limbs were injected with India ink. The vascularity of the peroneal tendons was examined in situ and the tendons were harvested and cleared using a modified Spalteholz technique. The vascularity of the cleared tendons was evaluated utilizing a dissecting microscope. The vascular supply of the peroneal tendons arises from two posterolateral vincula, one for the peroneus longus tendon and one for the peroneus brevis tendon. These vincula are supplied by branches of the posterior peroneal artery. A zone of hypovascularity within the peroneus brevis or peroneus longus tendon correlating with the site of peroneus brevis splits was not found. There was no relationship between increasing age of specimens and alteration in vascular supply.


Open total dislocation of the talus with extrusion (missing talus): report of two cases.

Two different methods of treatment for open dislocation of the extruded talus without soft tissue attachments (missing talus) were examined. In case 1, a 20-year-old man sustained an open total dislocation of the talus due to a motorcycle accident. The missing talus was found within 3 hr and replaced after thorough washing and debridement. Weightbearing was permitted at 20 weeks; however, the density of the talar body increased in the x-ray and nonweightbearing status was resumed. Reexamination at 2 1/2 years revealed that there was joint space narrowing on the x-ray and decreased pain with ambulation; the patient had returned to his job. In case 2, a 26-year-old man sustained an open total dislocation of the talus with a severe crush wound and impaired circulation to the foot. After thorough washing and debridement of the wound, the calcaneus and distal end of the tibia were aligned. The missing talus was found 3 days later, but not replaced. Weightbearing was allowed on the affected foot at 2 months; however, the patient felt pain at the joint surfaces and arthrodesis was consequently performed. At 2 1/2 years, the patient had a 4.0-cm leg length discrepancy in the involved extremity, but felt no pain when walking. Although reduction of the talus is ideal to preserve function and length of the extremity, several complications can occur. A review of literature on open total dislocation of the talus with extrusion was performed.


Achilles tendinitis.

Achilles tendinitis is a problem encountered frequently. There are certain anatomical and biomechanical principles that help explain the etiology of this entity. We prefer to separate our thinking into "insertional" and "noninsertional" Achilles tendinitis. This is helpful because it allows nonoperative and operative treatment to be problem specific and systematic.


[Pathophysiologic principles of metabolic syndrome. Consequences for early diagnosis and prevention].

The metabolic syndrome (syndrome X) is characterised by an association of elevated insulin levels, a tendency to obesity of the android type, a disturbance of lipid metabolism with elevated triglyceride levels and commonly associated hypertension. The underlying common cause of this syndrome appears to be insulin resistance of the skeletal muscles, which is related in particular to the non-oxidative glucose utilization on the part of the muscle. The molecular cause of this syndrome has not been clarified, but a defect in the signal transduction chain between the insulin receptor and glycogen synthase is suspected. Epidemiological studies have shown that the metabolic syndrome may be considered a preliminary stage of manifest type II diabetes. In addition, it appears to play a major role in the development of cardiovascular complications in certain high-risk groups.


[Metabolic syndrome and type-II diabetes. Relations to macroangiopathy].

Clinical and epidemiological findings over the last few years are increasingly pointing to a metabolic syndrome comprising major cardiovascular risk factors, which frequently characterizes type II diabetes and its preliminary stages. More recent studies have shown that insulin resistance is genetically determined and can be detected in a pre-diabetic stage long before diabetes mellitus becomes manifest. It is thus not surprising that a large percentage of patients with type II diabetes already have clear signs of arteriosclerosis at the time the diagnosis is made. The results of the Schwabing study II indicate a "point of no return" for the development of cardiovascular disease, which makes early and vigorous intervention involving all facets of the metabolic syndrome a matter of urgency.


[Hypertension in metabolic syndrome. Etiology and consequences].

Essential hypertension in patients with the metabolic syndrome is regularly associated with other metabolic disorders. Thus, most hypertensives are overweight and have a glucose intolerance, while many have concomitant hyperproteinemia and dyslipoproteinemia. Up until fairly recently, it was not known that so-called insulin resistance is a common denominator both of metabolic risk factors and hypertension. In recent years, our knowledge about insulin resistance has spawned an equally convincing and fascinating multidimensional concept which reveals and plausibly explains complex relationships between metabolism, hypertension and the coronary risk.


[Dyslipoproteinemia and metabolic syndrome. Effects of insulin resistance and hyperinsulinemia on lipid metabolism].

Insulin resistance and consecutive hyperinsulinemia in individuals with the metabolic syndrome are associated with dyslipidemia. This latter is characterised by hypertriglyceridemia and a diminishment of high-density lipoprotein (HDL) cholesterol in the plasma. In severe forms of insulin resistance, low density lipoprotein (LDL) cholesterol may also be elevated. Hypertriglyceridemia is due to an increase in the rate of synthesis of very low density lipoproteins (VLDL) in the liver, and a reduction in their breakdown by the lipoprotein lipase in non-hepatic tissue. Changes in VLDL metabolism are associated with a reduction in HDL concentrations. In addition, direct effects of insulin on the lipid metabolism have been described. Changes in lipid metabolism due to insulin resistance and hyperinsulinemia may be of significance for the atherosclerosis risk in patients with the metabolic syndrome.


[Ibuprofen--successful in activated arthrosis. Results of a administration study].

Within the framework of an observational study carried out on a national basis and involving some 4,000 patients, a total of 1,156 patients with activated arthrosis were treated with oral ibuprofen and observed over a period of three weeks. It was found that, at a dose of 600 mg tid, ibuprofen led to significant remission rates in terms of the symptoms pain at rest, pain on movement, tenderness, restriction of movement, swelling, joint effusion, and morning stiffness. After the third week of treatment, these rates reached 90%. In the first week, rapid onset of action within the first 30 minutes was noted in about 50%, which increased in the third week to 65%. Since at the same time the tolerability of ibuprofen was also found to be good--4% side effects--it can be recommended also for long-term use in this indication.


Microsurgical and angiographic analysis of anterior communicating artery aneurysms with associated anomalies.

A direct operation was performed on 110 patients with an aneurysm of the anterior communicating artery (ACoA). During the surgery, in 52% of the cases, the neck of the aneurysm was found at the junction of the A-1 segment and ACoA and they presented with a hypoplastic contralateral A-1 segment. Associated ACoA anomalies were seen in 13 (12%) of the 110 cases. The most common anomaly was duplication of the ACoA, found in 11 cases (10%). In 2 other cases triplicate ACoA was found. Preoperative bilateral carotid angiograms were reviewed and duplication of the ACoA associated with the aneurysms able to be pointed out on angiograms in 4 cases, retrospectively. The anatomical and radiological aspects of aneurysms with associated anomalies are also discussed.


[Diagnostic goals in aortic dissection. Value of transthoracic and transesophageal echocardiography].

The combination of different ultrasound techniques like transthoracic, suprasternal, subcostal and transesophageal echocardiography have a high sensitivity and specificity in the diagnosis of aortic dissection. The limitation of this combined ultrasound technique is related to the visualization of the ascending part of the aortic arch which, cause of the interposition of the trachea, can not be visualized completely. The beginning or the end of a dissection in this part of the aorta may be misinterpreted. False negative results are rare. False positive results due to artefacts resulting from reverberations in an ectatic ascending aorta have to be taken into account. The most important diagnostic aims in acute or chronic aortic dissection can be described: 1. confirmation of the diagnosis by visualization of the intima membrane, 2. the differentiation of the true and false lumen depending on visualization of spontaneous echocardiographic contrast thrombus formation, slow or reduced reversed flow, systolic diameter reduction and signs of entry jet into the false lumen, 3. detection of intimal tear, demonstrating communication by two-dimensional or color Doppler echocardiography, 4. determination of the extent of the dissection with classification according to DeBakey type I, II and III or Stanford A and B with differentiation to communicating or non-communicating dissection, antegrade or retrograde dissection limited to the descending aorta or expanding to the ascending aorta, 5. detection of wall motion abnormalities as a sign of preexisting coronary artery disease or myocardial ischemia due to ostium occlusion by an intimal flap, coronary artery rupture or collapse of the true lumen during diastole, 6. detection and grading of aortic insufficiency, 7. detection of side branch involvement by suprasternal, subcostal and abdominal sonography, which will gain the information which side can be chosen for cannulation or catheterization at the femoral artery, 8. detection of pericardial pleural effusion and mediastinal hematoma as a sign of emergency as rupture can occur within minutes. Without surgical intervention have be performed. Based on these informations, surgery can be performed in all acute situations in type A dissection without further investigations. This decision is particularly important in patients with signs of emergency like pericardial or pleural effusion or mediastinal hematoma.


[Acute and subacute dissection of the thoracic aorta: diagnostic importance of magnetic resonance tomography].

The purpose of this study was to retrospectively assess the reliability of ECG-triggered magnetic resonance imaging (MRI) for the diagnosis of acute and subacute thoracic aortic dissection and associated clinical epiphenomena. 67 patients were subjected to MRI; the diagnostic results were compared with morphological standards. 25 patients had type A, 12 patients type B dissection. In 30 cases a dissection was excluded. 17 patients with aortic dissection had acute onset of symptoms, 10 patients had subacute onset of symptoms. 17 patients revealed thrombosis of the false lumen, which was found in the descending aorta in 59% of the cases. Aortic regurgitation and pericardial effusion was most often associated with type A dissection (Table 1). Three patients were studied while on mechanical ventilation. Scan time for MRI ranged from 15 to 71 minutes with an average of 46 +/- 18 minutes. In this series no deleterious events were encountered related to MRI diagnostics. In contrast to previously published data using other noninvasive techniques the sensitivity of MRI was 100% for detecting a dissection in the ascending segment of the thoracic aorta. Moreover, the specificity of MRI for a dissection was 100% and thus higher than previously published data using transesophageal echocardiography. Sensitivity and specificity for detection and correct classification of type B dissection was 100% and 100% respectively (Table 2). In addition, MRI proved to be sensitive in detecting the formation of thrombus material in the false lumen of the ascending aorta (92%), the aortic arch (100%) and the descending segment (88%). Specificity for exclusion of suspected thrombus material even proved to be slightly higher with 100% in the ascending and descending aorta and 96.1% in the aortic arch (Table 3). The site of entry to a dissection was detected in 78%, with a sensitivity of 76% in the ascending and 92% in the descending aorta. The involvement of side branches in the dissecting process was identified in 60%. There were no false positive findings concerning side branch involvement. Aortic regurgitation and pericardial effusion were detected in 100% and 100%, respectively (Tables 1 and 2). MRI performed even in acute cases proved to be a atraumatic, safe and highly sensitive method to identify and classify acute and subacute dissections of the entire thoracic aorta. Limited patient access was not associated with an increased risk and mechanical ventilation did not interfere with MRI. These results may establish MRI as a valid and promising noninvasive technique to establish the diagnosis in patients with thoracic aortic dissection.(ABSTRACT TRUNCATED AT 400 WORDS)


[Surgical aspects of acute aortic dissection].

This paper highlights some of the surgical aspects of acute aortic dissections such as: emergency diagnosis, indications for surgery, reconstructive operative techniques, malperfusion phenomena and necessity for follow-up. Aortic dissection is caused by an intimal tear, called the "entry", and subsequent splitting of the media by the stream of blood. Two lumina are thus created, which may communicate through "re-entries". As this creates severe weakness of the aortic wall, rupture and/or dilatation are the imminent dangers of acute aortic dissection. Acute aortic dissection type A, by definition involving the ascending aorta (Figures 1 and 2), is an absolute indication for emergency surgical treatment, because its natural history shows an extremely poor outcome (Figure 3). Due to impending (intrapericardial) aortic rupture, it may be necessary to limit diagnostic procedures to a minimum. Transesophageal echocardiography is the method of choice for establishing a quick, precise and reliable diagnosis (Figure 4). In stable patients, computed tomography gives additional information about aortic diameters or sites of extrapericardial perforation. Digital subtraction angiography (DSA) shows perfusion of the lumina and dependent organs. The surgical strategy in acute aortic dissection type A aims at replacement of the ascending aorta. Reconstructive techniques have to be considered, especially in aortic valve regurgitation without annuloectasia (Figures 5 and 6). In recent times, the use of GRF tissue glue has reduced the need for teflon felt. Involvement of the aortic arch should be treated aggressively up to the point of total arch replacement in deep hypothermic circulatory arrest as part of the primary procedure (Figure 7). Malperfusion phenomena of aortic branches remain risk-factors.(ABSTRACT TRUNCATED AT 250 WORDS)


[Surgical therapy of thoracic aortic dissection].

Considerable surgical progress of treating aortic dissection has been achieved during the past decade. The emergency indication for acute dissection of the ascending aorta (type A according to the Stanford classification) is unquestioned while surgical treatment for acute dissection of the descending aorta (type B dissection) is mainly reserved for complicated cases. The major complication of acute operations--fatal hemorrhage from the suture line and secondary multi-organ failure--have been successfully reduced by a progress of cardiopulmonary bypass techniques, the introduction of cold cardioplegic myocardial protection, the development of modern suture materials and glues and last not least by a continuous intensive monitoring. Especially the introduction of the so-called french glue safely enabled both the closure of the false lumen as well as the strong reinforcement of the diseased aortic wall and seems to offer a reliable alternative to the application of multi-layered teflon strips. Since the principle of all reconstructive approaches in case of dissection consists of closure of dissected layers and the limited replacement of the segment that is susceptible to a rupture the exact readaptation and reinforcement of the diseased aortic wall represents a fundamental operative step. In type A operations the supracoronary aortic prosthetic replacement or the combined replacement of ascending aorta plus aortic valve followed by the reattachment of coronary arteries has become the standard operative technique. In fact, independently from the location of the primary intimal tear the operation has been traditionally limited to replace the ascending aorta in order to remove an aortic segment that is most likely to rupture. Yet an increasing number of follow-up investigations has demonstrated recurrence of dissection or an aneurysmatical dilatation of the false lumen in about 20% of patients treated with ascending aortic replacement. Consequently, repair of the aortic transverse arch and the radical elimination of the intimal entry is now favoured by an increasing number of surgeons. In addition to these various perioperative and intraoperative adjuncts the introduction of new imaging techniques, especially computerized tomography, magnetic resonance imaging and transesophageal echocardiography allowed to establish adequate therapeutical concepts on a more rational basis. Transesophageal echocardiography as a mobile diagnostic device enables investigators to perform a bed-side dynamic visualization of both the location and extent of a dissection, the evaluation of ventricular performance and aortic competence. Treatment of acute type B dissection is mainly conservative unless complications like intractable pain, aneurysmatic enlargement of the false lumen, ischemia of visceral organs or even rupture occur.(ABSTRACT TRUNCATED AT 400 WORDS)


Intraoperative echocardiography for diagnosis and treatment of aortic dissection. Utility of color flow mapping for surgical decision making in acute stage.

In the past eight years until July 1992, 92 patients were admitted in the acute state of aortic dissection within two weeks from the onset of symptoms. 41 were diagnosed as Stanford type A and 51 were type B by transthoracic and transesophageal echography, computer tomography, and surgery. Sensitivity of transesophageal echography to detect the intimal flap and the false lumen was 97.6% in patients with Stanford type A and 100% in patients with Stanford type B. The surgical decision making has been mostly depending on the transesophageal echographic diagnosis. When the intimal flap was detected in the ascending aorta (Stanford type A) surgery was performed in emergency regardless of any evidence of rupture, cardiac tamponade, and severe aortic regurgitation. When the aortic dissection was detected only in the descending aorta (Stanford type B) the main course of therapeutic strategy in our institute was medical treatment. Surgery was performed on 37 patients of type A and nine patients of type B with mortality of 18.9% and 55.5% respectively. Four patients of type A and 42 patients of type B were treated medically with a mortality of 75.0% and 2.2% respectively. The relatively large leakages from the anastomosis of the aortic clamp site were repaired secondarily in two patients, and fenestration of the superior mesenteric artery was performed on one patient due to ischemia of the small intestine depending on the intraoperative direct scanning of color flow mapping. Coronary artery involvement of dissection was strongly suspected in two patients by intraoperative transesophageal echography and aortocoronary bypass grafting was performed on these patients. Perfusion problems was encountered in five of 37 patients with type A aortic dissection (13.5%) during cardiopulmonary bypass. Intraoperative transesophageal echography could clearly detect the hemodynamic changes in the descending aorta resulting from inadequate perfusion which was useful for the management of perfusion control during cardiopulmonary bypass. Secondary repair of the aortic arch was required due to ischemia of the aortic arch vessels in two patients after the primary surgery. The extension of the dissection into the aortic arch vessels can be promptly diagnosed with the combination of transesophageal echography and transcutaneous echography. In conclusion, transesophageal Doppler echography is the most rapid diagnostic tool for decision making in acute aortic dissection, and intraoperative transesophageal echo can provide useful information to resolve the perfusion difficulties during cardiopulmonary bypass.(ABSTRACT TRUNCATED AT 400 WORDS)


A cylinder-shaped balloon catheter for the management of dissecting aneurysms in acute stage.

We developed a new procedure to close the entry of dissecting aneurysm in acute stage with a specially designed cylinder-shaped balloon catheter. The balloon catheter consists of 7F double lumen catheter and a silicone rubber balloon at the tip. The balloon has a central tube 14 mm caliber made of rigid silicone and it inflates into the shape of a cylinder with an injected solution. The central tube serves as a route for maintaining the aortic blood flow to the distal site. The catheter with a deflated balloon is inserted into the thoracic aorta ascendingly through a 14 or 16 mm caliber Dacron vascular graft sutured at the side of the distal aorta in a similar manner to intra-aortic balloon pumping. The tip of the catheter is carried to the entry tear of the pseudo-lumen. Then the cylinder-shaped balloon is inflated with solution. The entry is, therefore, closed with the side wall of the balloon and the blood stream into the dissected lumen is occluded while maintaining an aortic blood flow to the distal site. To prevent any possible occlusion due to thrombosis, some type of anticoagulant is administered via the catheter connected to a continuous injector. The healing process of the dissected lumen can be enhanced by injecting some type of coagulant directly into the lumen. The treatment is completed when the blood in the false lumen coagulates and stabilizes. The cylinder-shaped balloon is then deflated and the catheter withdrawn. The graft is removed and the stump is sutured.(ABSTRACT TRUNCATED AT 250 WORDS)


Long-term follow-up after separate replacement of the aortic valve and ascending aorta.

Between May 1974 and November 1991, 28 patients underwent a separate replacement of the aortic valve and the ascending aorta (20 male, eight female; 32 to 71 years old, x = 52 years). 23 patients were operated for ascending aortic aneurysm, three for chronic and two for acute aortic dissection type A. 17/18 patients living at the beginning of this study were re-investigated after a mean follow-up interval of 8.5 years postoperatively with DSA, thoraco-abdominal CT and echocardiography. 1/8 biological aortic valves and 1/20 mechanical valves had to be replaced (four years and two months postoperatively) for valve degeneration and paravalvular leakage respectively. Three patients developed a sinus of Valsalva aneurysm and were reoperated five, 9.2 and 9.3 years after primary repair. In all three patients histological signs of idiopathic degenerative media disease of the aorta were found. Two other patients presented with a perfused perigraft channel and therefore had to be reoperated. Patients with chronic aortic dissection type A and/or ascending aortic aneurysms presenting clinical or intraoperative signs of degenerative media disease of the aorta should undergo composite graft replacement to preclude formation of sinus Valsalva aneurysms.


[Meta-analysis of the prognosis of thoracic aortic dissection: changing mortality in the last four decades].

The acute dissection of the thoracic aorta is a potentially lethal event with a death rate of 1 to 2% per hour urging for undelayed diagnosis and adequate treatment. First, this paper highlights both the demographic characteristics and the classification according to anatomical and prognostic criteria, i.e. class I to III according to DeBakey and type A and B according to Daily (or Stanford). Moreover, the etiology of aortic dissection is explained, including factors such as degenerative changes of the aortic media layer, chronic trauma from hypertension, primary connective tissue disease and acute deceleration trauma. Second, the clinical criteria of acute (within 14 days of the index event) and chronic dissection (> 14 days) is discussed with respect to the current literature. The dominant part of this paper represents a meta-analytic approach comprising all available literature sources with respect to emerging changes in the prognosis of thoracic aortic dissection over 40 years as a function of either the type, the anatomic location, the acuity or the impact of medical or surgical treatment of this disorder. The meta-analysis revealed that in acute and chronic type A dissection medical treatment alone failed to lead to a significant improvement of 30 day-mortality rate (Tables 1 and 2, Figure 1). However, with surgical interventions the 30 day-mortality rate was continuously lowered from 60% to 10% within the past 30 years. A similar evolution was observed for the chronic type A dissection (Tables 3 and 4, Figure 2). Furthermore, the meta-analysis revealed that the acute type B dissection benefits from medical treatment, especially antihypertensive medication since the 30 day-mortality of 40% in 1960 decreased to less than 10% at present with monitoring and effective medication (Tables 1 and 2, Figure 3). In case of chronic type B dissection the literature survey revealed mortality numbers fluctuating between 2% and 20% without a clearcut beneficial effect of medical therapy throughout these years, though possibly revealing some advantage over surgical treatment. Thus, both for the acute and chronic type B dissection the antihypertensive therapy is considered treatment of first choice, whereas surgical interventions may be necessary for complicated and progressive cases. In summary, compared to the natural course of thoracic aortic dissection with only 10% survival-rate after one year of onset (Table 9, Figure 5), any effective mode of treatment may significantly lower the high spontaneous death rate.(ABSTRACT TRUNCATED AT 400 WORDS)


Political contributions from the health and insurance industries.

During a major election year, interest surges in discovering the sources of campaign funds for influential members of Congress and presidential candidates. This study traces the contributors from the health and insurance industries during the 1990 campaign and presents preliminary figures for the 1992 campaign. Health interests contributed $16.3 million to congressional candidates in 1990, many of whom sit on influential committees and subcommittees. The insurance industry gave $10.9 million that same year. In either case, more than half of the funds came from political action committees (PACs); the rest, from individuals. As of 30 June 1992 health industry PACs had given more than $8.3 million to candidates for federal office in the 1992 campaign; insurance PACs had contributed $6.4 million.


One approach to tracking state and local health spending.

National health system reform proposals continue to emphasize states' shared responsibility for their citizens' health care. In view of this increased interest, this Data Watch examines how much state and local governments spend for health care, using primarily data from the U.S. Bureau of the Census. Significant discrepancies exist between these data and other sources of state and local health spending data. Nevertheless, census data are the most comprehensive source of information on state and local spending. In the 1980s the gross rate of state spending on health was exceeded only by spending on corrections; later reports indicate that health has now overtaken corrections. Health and hospital spending varies widely among states, ranging from $1.79 per $100 of personal income in New York (after federal funding and charges are subtracted) to $0.36 per $100 in Nebraska. Continued work is needed to unravel the differences between data sources and to improve the collection and use of data at the state and local levels.


The concentration of health expenditures: an update.

An earlier study tracing trends in health spending from 1928 to 1980 found health expenditures concentrated among the top 1 percent of those spending money for health care. In an update to that study, the authors found that that trend toward concentration has increased. In 1987 the tope 1 percent of spenders accounted for 30 percent of health spending, up from 26 percent in 1970 and 29 percent in 1980. In contrast, the bottom half of the population in terms of spending accounted for only 3 percent of total spending in 1987. The average expenditure for the top 1 percent of spenders in 1987 was $47,331. Nearly half of those top spenders in 1987 were elderly. Also, more than 16 percent were black, up from nearly 10 percent in 1980.


Effect of Medicaid payment levels on access to obstetrical care.

Across the nation, the number of providers serving pregnant Medicaid clients has dropped precipitously. In an effort to retain providers, in 1986 the Maryland Medicaid program tripled reimbursement fees for deliveries. This raised Medicaid payments for perinatal care to levels roughly comparable to those paid by private insurers. Providers' participation can be measured using two criteria: the total number of participating providers in a given country and the number of deliveries performed by targeted providers. The fee increase was associated with an overall stabilization in the number of providers performing deliveries. Providers performed slightly more deliveries after the fee increase, relative to predictions derived from statistical models. One-quarter of all providers increased their participation on a scale commensurate with the fee increase.


Medicaid 2176 home and community-based care waivers: the first ten years.

Budget reconciliation legislation in 1981 created a waiver program whereby states could provide home and community-based care under Medicaid for certain populations. States spent nearly $1.7 billion on services delivered under these waivers, known as 2176 waivers, in 1991, compared with $3.8 million in 1982, when only six states were participating in the program. Although these programs have not been rigorously evaluated for effectiveness, they continue to be a popular approach to delivering care outside of institutions for various groups. Across all states, states spent 13.4 percent of their Medicaid long-term care dollars on care outside of institutions (which includes the 2176 waiver program).


Political evolution of federal health care regulation.

Although federal regulation of health care faces cultural obstacles and skepticism among policymakers, it has grown markedly over the past two decades. Beginning in the 1970s with decentralized programs aimed at regulating provider behavior (Health Systems Agencies and certificate of need) and budgets (state rate setting), health care regulation grew more centralized in the 1980s as federal policymakers expanded their influence on behavior (peer review organizations and medical practice guidelines) and budgets (Medicare prospective payment and the resource-based relative value scale). Behavioral regulation has increased the heavy micromanagement that providers face in the United States, while budgetary regulation falls well short of the fiscal macromanagement (global budgets, for example) that other Western nations use. As cost increases intensify, the coalitions that supported limited regulation as a compromise designed to forestall more threatening intrusions may yield to political pressure for firmer central budget controls.


Employer-sponsored health insurance in 1991.

Since 1987 the Health Insurance Association of America (HIAA) has documented features of employer-sponsored group health insurance through detailed surveys of over 3,000 U.S. firms. The 1991 employer survey reveals several noteworthy developments. The percentage of small firms (100 employees and under) that offer health insurance to their employees has declined since 1989. With a significant increase in health maintenance organization (HMO) market share, more than half (54 percent) of employees in employer-sponsored plans are now covered by managed care plans. Premiums increased 14 percent in 1991, showing identical increases for conventional, HMO, and preferred provider organization (PPO) plans. The percentage of employees in self-insured health plans decreased from 45 percent in 1990 to 40 percent in 1991.


The legislative battle over health services research.

Budget reconciliation legislation in 1989 created the new Agency for Health Care Policy and Research (AHCPR), which folded in the National Center for Health Services Research and Health Care Technology Assessment, among the law's other provisions. The creation of the new agency represented a shift in priorities toward outcomes and effectiveness research in medical practice and made explicit the federal government's role in developing practice guidelines. The new agency was born in the midst of an extraordinary bipartisan budget negotiation process in late 1989; its becoming linked to the contentious issue of physician payment reform nearly killed the new agency before it appeared. The narrative of political wrangling that resulted in the creation of AHCPR spans Capitol Hill, the White House, the agencies of the Department of Health and Human Services, and renowed health services researchers on either coast and in Washington, D.C.


A federal/state partnership for health system reform.

In view of the continued lack of consensus regarding health system reform, a new approach is needed to the pluralism that characterizes the U.S. political scene. A two-step strategy can help to break the deadlock around health care financing and provision: a framework around which to shape federal/state responsibility for health care and a process to ensure that policy is translated into action. This strategy, called a federal/state compact for health, builds on actions already under way in several states and represents a process that is both incremental and comprehensive in nature. The federal government would take the lead regarding policy making, financing, and establishing benefits. The states would administer the program with flexibility similar to that existing in Canada's provinces.


The role of federal waivers in the health policy process.

Federal waiver programs enable states to bypass the requirements of federal programs such as Medicare and Medicaid to experiment with different ways of financing, organizing, and delivering health care. In tracking waiver activity from 1980 to 1990, the authors found that federal involvement with waivers lost momentum during the latter part of the 1980s, while state involvement increased. Three key issues dominate the discussion of waivers: administrative control, the role of the states, and the ability to evaluate demonstration waivers. Examination of the chronology of waiver activity suggests the emergence of a new era, wherein federal control reemerges as a way to counter the increased fragmentation of health policies among states. If this is the case, four areas need to be addressed: (1) balance of political and research objectives; (2) administrative flexibility for states; (3) careful scrutiny of rules; and (4) increased accountability. These recommendations can guide the federal government, with the states as partners, in its attempt to regain momentum in the use of waivers to expand the knowledge base.


The courts and health policy: strengths and limitations.

In recent years the nation's courts have expanded their influence in health policy in four areas: reviewing insurers' coverage decisions, deciding the adequacy of Medicaid payment rates to hospitals and nursing homes, arbitrating hospital mergers, and assessing hospitals' tax-exempt status. The major problem with developing health policy through the courts is that the courts' focus will be the concerns of the individuals or groups involved in specific cases, not the broader implications and overall objectives of the health care system. As alternatives to litigation to resolve policy conflicts, scholars have suggested negotiation, binding arbitration, clarification of legislative language, administrative courts, contract revision, and general restructuring of the decision-making process.


The physics of esophageal dilatation.

The use of dilators to enlarge esophageal strictures is an old and widely used technique. New technology and designs permit reduced trauma and complications and may ultimately extend the durability of the procedure. Understanding the physics of dilators and their use is essential for clinicians to achieve maximum therapeutic benefit for their patients.


Balloon dilatation of benign esophageal stenoses.

The traditional nonoperative management of benign esophageal stenoses has been bougienage; recently, balloon dilatation has become available. Balloon dilatation can be accomplished with balloons that are passed over a guide-wire or with balloons that are passed through the working channel of an endoscope. In the present paper, the methodologies for the use of these two types of balloons are described and the literature reviewed. Balloon dilatation appears to be an efficacious and a safe alternative to bougies.


Mercury bougie dilation of benign esophageal strictures.

Dilation with mercury filled bougies is the oldest and simplest technique available for treatment of benign esophageal strictures. In the majority of patients, mercury-filled dilators are effective and quite safe. Dilation is successful in 80-90%, and the rate of complication is less then 0.2%. Maloney dilators have superseded Hurst dilators because their tapered, flexible tip allows better guidance of the dilators into the lumen of the stricture. Several cautions are in order when using Maloney dilators. Dilation of difficult strictures should be observed by fluoroscopy to prevent misdirection of the dilator and esophageal perforation. Where possible, Maloney dilators should not be used to treat narrow, elongated, or angulated strictures. Dilation need not be rushed. Treatments may be repeated over months to years, both to achieve symptomatic relief initially and to maintain that state. Finally, patients susceptible to endocarditis require antibiotic prohylaxis prior to treatment.


Surgical management of esophageal strictures.

Benign esophageal strictures may be caused by numerous disorders, but more than 90% of them are due to severe gastroesophageal reflux or ingestion of lye. A new classification of the severity of the stricture is proposed, based on the endoscopic and radiological evaluation of three parameters: internal diameter, length of the stricture and ease or difficulty of dilatation. In patients with strictures secondary to reflux, initial treatment includes periodic dilatation. Grade I and II strictures require esophageal resection. In grade III patients, bile diversion or esophageal resection should be performed. Caustic ingestion produces a wide spectrum of tissue damage in the upper digestive tract ranging from minimal chemical burn to an extensive and massive necrotic lesion. The basic and main treatment in patients with an established esophageal stricture is periodic dilatation avoiding, if at all possible, any kind of surgery. In patients with grade III stricture, colonic interposition between cervical esophagus and stomach or duodenum is preferred, treating the damaged esophagus by resection or leaving it "in situ". Psychiatric evaluation is mandatory in these cases.


Significance of venous drainage for small-bowel allografts.

Small bowel transplantation has proved feasible in rats and in larger animal, but several important questions have yet to be answered before it becomes a potential therapy in man. One consideration is the site of venous outflow of the allograft. Portal drainage, however, re-establishes the physiological route of venous outflow, while systemic drainage creates a partial mesocaval shunt, the metabolic consequences of which have not been studied in detail. Using the canine model in partial mesocaval shunt and porta-caval shunt, we compared the metabolic and histological changes following each shunt. The metabolic changes in Eck were hyperammonemia and amino acid imbalance, while those in partial mesocaval shunt were similar to controls. The histological appearance of the liver in Eck was atrophy, fatty infiltration and deglycogenation, while that in partial mesocaval shunt was completely normal except for minimal fatty degeneration. These data suggest that there is no metabolic or histological disadvantage of systemic venous drainage as compared with control, and because of its technical simplicity, systemic venous drainage may be preferable in small bowel transplantation.


Esophagogastrectomy: a consecutive single-center series.

We present a 7-year consecutive, nonselected, single-center series of patients (n = 140) submitted to surgery for esophageal or upper gastric malignancy. Follow-up data are complete for 96.4% of patients. Of 114 intrathoracic anastomoses, 74 (65%) were esophagogastric and 40 (35%) were esophagojejunal. Unresectable lesions were present in 26 (19%) patients. Age (mean +/- sd 64.6 +/- 11.1 years), and sex distribution were similar in all groups, while 36% of patients were over 70 years. There was no significant difference in the time from the onset of symptoms to presentation between the groups (p < 0.05). The values of admission hemoglobin, serum albumin, PaO2 or peak expiratory flow rate did not correlate with survival. There was no significant difference in 30-day operative mortality between the three procedures - esophagectomy 5%, thoraco-abdominal gastrectomy 10.8% and unresectable 11.5% (p > 0.05). The incidence of respiratory complications was the same whether a right (30%) or left (35%) thoracotomy was performed. Some 33% of patients were discharged from hospital after 14 days and 72% after 21 days (12.9% died in hospital). One-year survival was 33.4% for esophagectomy, 37.5% for total gastrectomy and 6% for unresectable lesions. The esophagectomy versus total gastrectomy survival curves were not significantly different, but there was a significant survival advantage when patients undergoing esophagectomy were compared with those who had unresectable tumors (0.02 > p > 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Spontaneous bacterial peritonitis in cirrhosis: clinical and laboratory features, survival and prognostic indicators.

This is a retrospective study of 35 patients with spontaneous bacterial peritonitis and liver cirrhosis identified between 1981 and 1989. The mean age of all patients was 44 years, with a range of 16 to 68. Criteria for spontaneous bacterial peritonitis included either a positive ascites culture with a polymorphonuclear cell concentration greater than 250 cells per mm3 (18 cases) or a negative ascitic fluid culture with a polymorphonuclear cell count greater than 500 cells per mm3 and no evident intra-abdominal source of infection (17 cases). Twenty-one patients were male and 14 female. The most frequent presenting symptoms were abdominal pain and fever, noted in 20 (57%) and 19 (54%) patients, respectively, while 5 patients (14%) were completely asymptomatic. The overall mortality in this series was 54% (19 of 35 patients). The presence of encephalopathy or renal insufficiency was associated with a high mortality rate (73% and 87%, respectively). Encephalopathy was present in 67% of the non-survivors, but in only 25% of the survivors (p < 0.0025); likewise, renal failure was observed in 68% of the non-survivors, but in only 12.5% of those who survived (p < 0.001). The use of newer-generation cephalosporins and penicillins led to a diminished mortality (42%) as compared with that (64%) observed in patients treated with conventional antibiotic regimens.


Reappearance of vanished bile ducts.

A 36-year-old Surinam woman with a severe form of toxic epidermal necrolysis of unknown origin is presented. Skin lesions healed gradually without scarring within 3 to 4 weeks, but eye lesions progressed to symblepharon and corneal opacification, resulting in almost complete blindness. In addition, toxic epidermal necrolysis was associated with severe intrahepatic cholestasis caused by vanished bile duct syndrome; viral hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis were excluded. After about six months, intrahepatic chole-stasis improved spontaneously and a third liver biopsy taken after 51 weeks of illness revealed that the bile ducts had reappeared. At present, the patient is relatively well, with no jaundice, although parameters of cholestasis are still elevated: Alkaline phosphatase three times, and gamma GT thirty times the normal values. This sequence of events has to our knowledge never been reported in the literature.


Splenic hyperkinetic state and splenic artery aneurysm in portal hypertension.

Forty-eight out of six hundred and thirty patients with portal hypertension undergoing a celiac angiography series were diagnosed as cases of splenic artery aneurysm during the period 1977-1988. The case-control study of patients with portal hypertension with splenic artery aneurysms and those without was designed to characterize the angiological features. The splenic arterial flow was assessed by measuring the radii of the splenic arteries on celiac arteriograms. In the portal hypertensive patients with splenic artery aneurysms, the splenic artery was larger (p < 0.05) and the splenic arterial flow greater (p < 0.05), and these patients were in a more hyperkinetic state, than were those with no splenic artery aneurysm. The study suggests that splenic artery aneurysms in cases of portal hypertension may be the consequence of a hyperkinetic state in the spleen.


Antineutrophil cytoplasmic autoantibodies (ANCA) in acute pancreatitis.

Antineutrophil cytoplasmic autoantibodies, which are now considered reliable serological markers of acute necrotizing vasculitic diseases, were measured in 11 patients with acute necrotizing pancreatitis and 12 patients with acute interstitial pancreatitis. When tested by indirect immunofluorescence, none of the sera was positive for diffuse cytoplasmic staining, and none was positive for perinuclear staining of antineutrophil cytoplasmic antibodies. Also by the sensitive enzyme-linked immunosorbent assay, none of the sera was positive when purified alpha-granule fraction of granulocytes was used as an antigen. We can therefore conclude that neither the diffuse cytoplasm-reacting, nor the perinuclear form of antineutrophil cytoplasmic antibodies, is involved in cases of acute pancreatitis.


Double-blind randomized clinical trial comparing neomycin and placebo in the treatment of exogenous hepatic encephalopathy.

Hepatic encephalopathy due to cirrhosis is frequently precipitated by exogenous factors, and the effectiveness of a specific treatment with neomycin sulfate has so far not been submitted to clinical trials. Over a period of five years, 102 cirrhotic patients developed hepatic encephalopathy at admission or during hospitalization, and 39 were randomized for treatment with either neomycin sulfate or placebo. Exclusion criteria were: 1. current usage of specific treatment for hepatic encephalopathy, 2. chronic hepatic encephalopathy and 3. multiple organ failure syndrome associated with hepatic encephalopathy. The group of excluded patients (n = 63) was compared with the randomized group (n = 39), and no statistical differences were found regarding sex and age distributions, Child-Pugh classification, etiology of cirrhosis, percipitating factors and grade of hepatic encephalopathy. These same parameters were also comparable among the 20 patients who received active neomycin and the 19 who were treated with placebo. The therapy for hepatic encephalopathy consisted in the control of precipitating factors associated with 6 g of neomycin sulfate "per os" or placebo. Therapeutic failure and death by the fifth day of treatment, occurred in four patients (10.2%), two in each of the randomized groups. The time elapsed between the initiation of the therapeutic procedure and regression to grade zero of hepatic encephalopathy was 39.11 +/- 23.04 hours for the group of active neomycin, and 49.47 +/- 21.92 hours for the placebo group, but this difference did not achieve statistical significance.


Comparative effects of 5% ethanolamine oleate versus 5% ethanolamine oleate plus 1% polidocanol for sclerosing esophageal varices.

Sixty-six patients with portal hypertension and esophageal varices due to liver cirrhosis were randomized to receive either 5% ethanolamine oleate (EO) or 5% EO plus 1% polidocanol (EOP) as a sclerosant for endoscopic injection sclerotherapy (EIS). The two groups were well matched with regard to age, sex and the severity of liver disease. In no patient in the two groups was there any major complication, such as esophageal perforation or esophageal bleeding. Eradication of esophageal varices was attained with an average of 4.7 and 4.3 sessions of endoscopic injection sclerotherapy in the ethanolamine oleate and polidocanol groups, respectively. Data on one patient in the ethanolamine oleate group had to be excluded because he left the hospital after 2 sessions of endoscopic injection sclerotherapy. Esophageal ulcers occurred earlier in the polidocanol group (after an average of 2.8 weeks) than in the ethanolamine oleate group (3.8 weeks), the difference being statistically significant (P < 0.01). The rate of occurrence of esophageal stricture requiring more than 2 sessions of bougienage was significantly (P < 0.01) higher in the polidocanol group (16/33, 48%) than in the ethanolamine oleate group (4/32, 12%). This study suggests that the two sclerosants have equal efficacy for treating patients with esophageal varices. With polidocanol there was ulceration and stricture in the distal esophagus.


Importance of direct hepatocytolysis by liver macrophages in experimental fulminant hepatitis.

When lipopolysaccharide was administered to mice that had been injected with heat-killed Propionibacterium acnes, most of them died of massive liver necrosis. Previously, we demonstrated that a soluble hepatocytotoxic factor released by liver adherent cells fully activated by both P. acnes and lipopolysaccharide was attributable to the late stage of this severe liver injury. In this report, we focused on the hepatocytolysis by these liver adherent cells in a cell-cell interaction manner. Shortly after stimulation with lipopolysaccharide, the P. acnes-elicited liver adherent cells almost completely killed the hepatocytes prepared from both normal syngeneic mice and P. acnes-treated ones. Since P. acnes-elicited liver adherent cells also proved to produce various kinds of cytokines in a short time, the role of cytokines in this liver injury was analyzed. Only TNF-alpha enabled the P. acnes-elicited liver adherent cells to kill hepatocytes prepared from the same mice, but none from the normal ones. These results suggest that the liver adherent cells accumulated and partly stimulated by P. acnes-treatment might rapidly lyse the autologous hepatocytes once triggered by lipopolysaccharide and that the TNF-alpha these liver adherent cells produced might upregulate their own hepatocytotoxic ability.


Protecting against the acid aspiration syndrome in adult patients undergoing emergency surgery.

This paper has studied the effect of i.v. cimetidine and ranitidine, given 1 h prior to anesthesia, on gastric volume and pH in three homogeneous groups undergoing emergency surgery. Group I (10 patients) received placebo, group II (20 patients) cimetidine 400 mg in saline solution, and group III (20 patients) ranitidine 150 mg in saline. Standardised premedication was administered and anesthesia induced. Immediately after tracheal intubation the stomach contents were aspirated and analysed for volume and pH. There were no significant differences in gastric volume among the three groups. However, treated patients had significantly elevated pH as compared with the control group and the number of patients at risk (pH < 2.5 and volume > 25 ml) was significantly smaller at 20% and 15%, respectively, than in the control group (40%). It is concluded that cimetidine 400 mg, and ranitidine 150 mg i. v., given about 70 min. prior to induction of anesthesia may decrease the risk of the acid aspiration syndrome in emergency operations.


Gallstone ileus.

A retrospective analysis of 74 patients with gallstone ileus detected during the period between 1975 and 1987 was performed at the Surgical Department. The group comprised 55 females and 19 males, with a mean age of 64.8 years. Previous biliary symptoms had been observed in 76% of the cases and in 58% there had been concomitant disease. The main duration of symptoms previous to admission was 3.4 days. In 85% of the cases complementary diagnostic procedures were performed. The triad of air in the biliary tract, air-fluid levels and ectopic stone was found in only 9.5% of the cases. The preoperative diagnosis of gallstone ileus was made in 31% of the patients. The preoperative period was 2.2 days. The main surgical procedure was enterolithotomy in 92% of the cases, the site of impaction being the terminal ileum in 65%. Only in 1 case was simultaneous biliary tract surgery and enterolithotomy performed. Overall, the 30-day postoperative mortality rate was 13.5%, with intra-abdominal sepsis as the main cause of death. Sixteen patients were submitted to biliary surgery 2 to 6 months later, and no deaths occurred.


Cholangiocellular carcinoma in the caudate lobe with intraluminal growth in the extrahepatic bile duct.

A case of cholangiocellular carcinoma in the caudate lobe with intraluminal growth in the extrahepatic bile duct is reported. The main tumor in the caudate lobe was detected by computed tomography and angiography, and two intraluminal tumors at the hepatic hilus and at the root of the right posterior segmental duct were well demonstrated by cholangiography and percutaneous transhepatic cholangioscopy. Independent total caudate lobectomy with bile duct resection was performed. Cholangiocellular carcinoma of the liver with intraluminal growth in the extrahepatic bile duct is very rare and has not been reported in the literature. Independent caudate lobe resection requires a rather complicated technique. However, this method has the advantage of reducing to a minimum the hepatic volume to be resected, and is useful for poor-risk patients or for cases with localized carcinoma at the hepatic hilus.


Polymorphonuclear count in ascitic fluid after laparotomy in cirrhotic patients.

In order to establish whether an ascitic polymorphonuclear count greater than 250/mm3 remains a diagnostic criterion for postoperative bacterial peritonitis, a prospective study of 16 patients with cirrhosis and ascites undergoing hepatectomy (n = 4), portocaval shunt (n = 5) and biliary and digestive surgery (n = 7) was carried out. Sixty-four consecutive specimens of ascitic fluid were obtained through abdominal one-way suction tubes left in situ. In 17 (26%) specimens, ascitic fluid was blood stained and the polymorphonuclear count was unreliable; none of these specimens demonstrated positive ascitic fluid culture. In the remaining 47 specimens the polymorphonuclear count ranged from 5 to 5,920/mm3. Positive ascitic fluid culture was significantly higher in polymorphonuclear > or = 250/mm3 group (5/13: 38%) than in polymorphonuclear < 250/mm3 group (2/34: 6%) (p < 0.02). These results suggest that, as in non-operated cirrhotic patients: (a) polymorphonuclear count should be taken in account in the diagnosis of postoperative bacterial peritonitis; (b) polymorphonuclear count greater than 250/mm3 is a good criterion for the diagnosis of bacterial postoperative peritonitis.


Gastric volvulus complicating myotonic dystrophy.

Myotonic dystrophy is an autosomal inherited disorder of both striated and smooth muscle, and is considered to be a rare cause of gastrointestinal dilatation and abnormal peristalsis. We report on a patient with myotonic dystrophy complicated by gastric volvulus. A 57-year-old female with myotonic dystrophy suddenly developed abdominal pain, nausea and vomiting. X-ray examinations revealed gastric dilatation and pyloroantral obstruction, consistent with acute gastric volvulus. The patient underwent successful emergency gastrectomy. Gastric volvulus is often an unrecognized surgical emergency, but its clinical and radiographic features are so characteristic that accurate diagnosis is possible if the condition is kept in mind. Thus, the clinician should consider the possibility of gastric volvulus when evaluating gastrointestinal complaints in patients with myotonic dystrophy.


[Activation of N-myc gene in leukemia cell lines derived from spontaneous murine lymphomas].

MuLV-integration sites were analyzed on seventeen thymic leukemia cell lines which have been established from spontaneous thymic leukemias in AKR mice and bone marrow chimeras. Three proviral integration sites were identified; near c-myc, N-myc and pim-1. Among them the integrations near the N-myc were analyzed. Two cell lines from AKR and a cell line from [(BALB/c x B6) F1-->AKR] bone marrow chimera contained the proviral integration near N-myc. In all three cell lines the integration of the provirus was found 18 to 20 bp downstream of the translational termination codon. The partial sequence analysis of the integrated LTR cell line established from AKR thymic lymphomas was the same as AKV. In contrast, the LTR integrated in a cell line from a bone marrow chimera was different from that of MuLV so far reported.


[An electron microscopic study of axonal dystrophy in the gracile nucleus of vitamin E deficient and normally aging rats].

Light and electron microscopic studies were carried out on the axonal dystrophy (AD) appearing in the gracile nucleus of normally aging and vitamin E (VE) deficient rats aged 18, 33, and 48 weeks. In both of 2 groups, AD was observed in axon terminals (AT) and axons. The accumulations of mitochondria, various types of dense bodies and tubular structures were common to both dystrophic AT and axons of normally aging and VE deficient rats. Synaptic vesicle-like vesicles, however, were scattered in dystrophic AT and neurofilaments in some of dystrophic axons increased. The incidences and mean areas of AD in VE deficient rats increased with aging much more than in normally aging rats. No essential ultrastructural differences of AD were observed in VE deficient and normally aging rats, but, structural changes of AD were more advanced in VE deficient rats. These results suggest that the formation of AD in AT and axons is accelerated by VE deficiency.


[Electrical tinnitus suppression--a comparative study of clinical trials and animal experiments].

Electrical tinnitus suppressor was newly developed and clinical study of electrical tinnitus suppression was discussed. Tinnitus was treated with this prototype suppressor in 38 ears out of 34 outpatients. Tinnitus was suppressed during electrical stimulation in all patients. After cessation of electrical stimulation, in 5 ears out of them tinnitus has disappeared at least for more than six months. In 12 ears it made tinnitus more than 10 dBHL softer for the following period, about six months. Hearing was unchanged in all patients. To know the mechanism how electrical stimulation of the cochlea suppressed tinnitus, animal experiments using a single fiber recording technique were made. A positive direct current on the cochlea suppressed the spontaneous activity of the cochlear nerve fiber, while a negative direct current increased the spontaneous activity. An alternative current on the cochlea increased the spontaneous activity of the cochlear nerve fiber. These electrical effects on the spontaneous activity were temporary. Therefore, after cessation of electrical stimulation on the cochlea, changed spontaneous activity restored to the level of prestimulation. Comparing temporary electrical effects on the spontaneous activity of cochlear nerve fiber with a longer suppression on tinnitus, tinnitus suppression following electrical stimulation of the cochlea was not thought to occur at the level of cochlea, but at auditory central nervous system.


[Localization of human sterol carrier protein 2 gene and cDNA expression in COS-7 cell].

Sterol carrier protein 2 (SCP2) is known to be an important polypeptide in intracellular sterol and lipid movement. Here are reported the cloning and expression of a cDNA encoding human SCP2, and the assignment of SCP2 gene to human chromosome 1. The 1,229 bp cDNA contains an open reading frame and the encoded polypeptide consists of 143 amino acids. This polypeptide is very similar in amino acid composition to human, bovine and rat liver SCP2. The deduced amino acid sequence of this cDNA has a 20-residue amino-terminal leader sequence with mature SCP2. Northern blot analysis suggests that there are 1.8 kb and 3.2 kb mRNA species in human liver poly (A)+RNA. PCR analysis of human x rodent somatic cell hybrid panels indicates that the gene encoding SCP2 is on human chromosome 1. Transient expression of the human liver SCP2 cDNA in COS-7 cells shows a 15.3KDa polypeptide and increased amounts of a 13.2KDa polypeptide. Coexpression of the SCP2 cDNA with cholesterol side-chain cleavage enzyme and adrenodoxin cDNAs resulted in a 2.5-fold progestin synthesis in comparison with that of the steroidogenic enzyme system alone. These findings suggest that SCP2 plays a role in regulating steroidogenesis, among other possible functions.


Of palindromes and peptides.

On the average, 30% of the residues in a protein are members of peptidic palindromes, tripeptidic and longer. This percentage may go up to 50% in histones and certain other DNA binding proteins. The longest peptidic palindrome encountered thus far was 14 residues in length. However, there is every reason to expect even longer peptidic palindromes in other proteins not yet analyzed.


On genetic components in autoimmunity: a critical review based on evolutionarily oriented rationality.

The immune system furnishes the organism with the utmost effective defence mechanisms against "foreign" and changes in "self" without doing self-harm. However, optimized efficacy in the defence against the immense variety of "foreign" antigens generates a higher risk for inadvertent self challenge. Such inherent short-comings are the inevitable burden traded for the benefits of an optimally organized defence system. The central molecules involved in specific immune reactions include antigen receptors of B and T lymphocytes, and antigen-presenting proteins encoded by the major histocompatibility complex (MHC; in man HLA). The genetics and evolution of these multigene families is discussed here with respect to their potential contributions to disturbances of "self" recognition. Simple molecular biological tools and procedures for efficiently screening the immunologically relevant genes are described.


A 47,XXY female with unusual genitalia.

A 47,XXY karyotype was found in a 6-year-old girl. The patient had female external genitalia, clitoromegaly, remnants of the ductus mesonephricus, uterus, and gonads in the labia majora which were determined to be testes by histology. Cytogenetic and DNA analyses suggest that the Y chromosome had a normal structure and that both X chromosomes were of maternal origin. The unusual clinical findings in the patient are discussed.


A familial mutation in the testis-determining gene SRY shared by both sexes.

A familial mutation in SRY, the gene coding for the testis-determining factor TDF, was identified in an XY female with gonadal dysgenesis, her father, her two brothers and her uncle. The mutation consists of a T to C transition in the region of the SRY gene coding for a protein motif known as the high mobility group (HMG) box, a protein domain known to confer DNA-binding specificity on the SRY protein. This point mutation results in the substitution, at amino acid position 109, of a serine residue for phenylalanine, a conserved aromatic residue in almost all HMG box motifs known. This F109S mutation was not found in 176 male controls. When recombinant wildtype SRY and SRYF109S mutant protein were tested in vitro for binding to the target site AAC AAAG, no differences in DNA-binding activity were observed. These results imply that the F109S mutation either is a rare neutral sequence variant, or produces an SRY protein with slightly altered in vivo activity, the resulting sex phenotype depending on the genetic background or environmental factors.


Analysis of segregation and expression of an identified mutation at the neurofibromatosis type 1 locus.

A previously identified complex mutation, affecting exon 28 of the neurofibromatosis type 1 gene, was employed for the analysis of the expression pattern in primary cultures of neurofibroma cells and melanocytes from a café-au-lait macule of the patient, respectively. Reverse transcription and subsequent polymerase chain reaction amplification of the segment carrying the mutation revealed that both alleles were expressed in both cell types analysed, thus excluding loss of heterozygosity in this particular instance. Segregation of the alleles of the intragenic Alu sequence length-polymorphism disclosed the paternal origin of the mutated allele. Detection of this mutation was also used for presymptomatic direct DNA diagnosis in the younger child of the patient.


Bloom's syndrome. XVIII. Hypermutability at a tandem-repeat locus.

D1Z2 is a highly polymorphic DNA locus composed of a tandem of repetitive units. Its molecular constitution has been examined in 61 clonal cell lines selected at random from two lymphoblastoid cell lines (LCLs), each of which had been proliferating in vitro for several hundred days. Thirty-three of the cells were selected from an LCL derived from the blood of a person with Bloom's syndrome (BS), and the others from a normal person. A total of 20 distinctive band alterations in D1Z2 were observed, all in BS cells: appearance of a novel band(s); disappearance of a band(s), or alterations in the intensity of a band(s). Unequal sister-chromatid exchange giving rise to intra-locus mutation is considered the most plausible explanation for the accumulation of the changes detected.