DNA-testing for Huntington's disease in The Netherlands: a retrospective study on psychosocial effects. Presymptomatic DNA-testing for Huntington's disease has made it possible to predict whether or not at-risk individuals are gene-carriers with a reliability of about 98%. In our retrospective study of 18 tested individuals, most of the newly identified carriers function apparently well. They use avoidance and repression of affect as psychological defense strategies. However, 8 out of 9 non-carriers do not experience the expected relief about their test results. They experience survivor guilt and emotional numbness and find it difficult to cope with the effects of the test results on the family system. The partners of gene-carriers are at risk of becoming emotionally isolated by putting aside their own feelings for fear of seeming self-centered. Appreciation of these effects on tested individuals is important and professional support is needed to prevent post-traumatic stress disorders. Whatever the test result may be, the working through process may take years rather than months. These findings have important implications for patient care and necessitate an extended period of observation after presymptomatic testing.


Mivacurium chloride: a study to evaluate its use during propofol-nitrous oxide anaesthesia. We assessed the neuromuscular and cardiovascular effects of mivacurium chloride, a neuromuscular blocking agent, in 33 patients during propofol-nitrous oxide anaesthesia. Neuromuscular function was assessed with supramaximal stimuli of the ulnar nerve, using surface electrodes at the wrist, with repeat trains of four. Mivacurium given as a bolus of 0.15 mg.kg-1 (ED95 x 2) was found to be haemodynamically stable. Intubating conditions assessed at 2 and 2.5 min were either good or excellent. All patients developed a block of 100% in a mean (SD) time of 105 (34) s. There were mean (SD) intervals of 12 (2.4) min before the reappearance of the first twitch of the train of four (T1) following the bolus dose, and 15.8 (3.1) min for the T1 to reach 25% of its control value (TC). Seventeen patients received an infusion of mivacurium to maintain neuromuscular blockade (T1:TC 10-20%) with a mean (SD) infusion rate of 6.9 (2.2) micrograms.kg-1.min-1. Recovery from neuromuscular blockade was assessed with spontaneous offset or augmented with edrophonium following either the initial bolus or an infusion. Following a bolus it took a mean (SD) of 26.2 (3.7) min for the fourth twitch of the train of four (T4):T1 ratio to reach 0.7. In patients receiving an infusion with spontaneous offset it took a mean (SD) time of 12.0 (2.2) min to reach the T4:T1 ratio of 0.7 from a T1:TC value of 8.8. Edrophonium significantly decreased the recovery time in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Ondansetron does not affect alfentanil-induced ventilatory depression or sedation. Ondansetron is a selective 5-hydroxytryptamine type 3 receptor antagonist effective as an antiemetic in patients experiencing post-operative or cancer chemotherapy-induced nausea and vomiting. Currently, no information is available regarding the interaction of ondansetron with opioids, although a serotonin antagonist might be expected to modify some opioid actions. This study was designed to measure the effects of ondansetron on alfentanil-induced ventilatory depression and sedation in healthy male volunteers. Ventilatory drive (measured as the end-tidal CO2 necessary to produce a minute ventilation of 15 l/min) was determined in 29 subjects using a modification of the Read rebreathing technique. Sedation was measured by asking the subjects to complete visual analog scales. Alfentanil was administered as a bolus (5 micrograms/kg) followed by a continuous infusion (0.25-0.75 micrograms.kg-1.min-1) for at least 90 min. Study medication (ondansetron 8 or 16 mg or vehicle placebo) was then administered in a randomized, double-blind manner, and the alfentanil was infused for an additional 15 min. Measurements of ventilatory drive and sedation were made at baseline, during alfentanil infusion, after study medication, and at 30-min intervals after alfentanil was discontinued. Alfentanil produced significant ventilatory depression (P less than 0.001) and sedation (P less than 0.001) in all three groups. Neither placebo nor ondansetron produced further change in the intensity of either alfentanil effect. After discontinuation of the opioid, both ventilatory depression and sedation decreased, and the rate of recovery was not significantly different between groups. The data indicate that alfentanil-induced sedation and ventilatory depression are not significantly affected by the subsequent administration of ondansetron.


Left ventricular hypertrophy in rabbits does not exaggerate the effects of halothane on the intracellular components of cardiac contraction. Inhalational anesthetics and ventricular hypertrophy have adverse effects on cardiac muscle contraction. The effects of 1, 2, and 3% halothane on the contractile protein and sarcoplasmic reticulum, but not the sarcolemma, were examined in normal left ventricular tissue from rabbits that underwent a sham surgical procedure (n = 5) and in left ventricular hypertrophied tissue from surgically induced aortic coarctation (n = 7). Muscle samples were mechanically "skinned" to disrupt the sarcolemma. Fiber bundles were mounted in photodiode transducers and bathed in a series of solutions designed to examine the contractile protein [Ca2+]-tension responses or to examine Ca2+ storage by and release from the sarcoplasmic reticulum. Hill equation analysis of the [Ca2+]-tension relationship of the contractile protein was performed. Compared to normal muscle, hypertrophied muscle was associated with an 8.2% decrease in the [Ca2+] necessary for 50% maximum tension (more sensitive to Ca2+) (P less than 0.001) and an increase in the slope constant of 23% (P less than 0.001). In normal and hypertrophied tissue, each 1% of halothane incrementally decreased the contractile protein response to maximal [Ca2+] by 5% (P less than 0.01), increased the [Ca2+] at 50% maximum tension by 5% (P less than 0.01), and had no effect on the slope of the Hill equation. Halothane also inhibited Ca2+ storage by the sarcoplasmic reticulum. In normal muscle, 1, 2, and 3% halothane decreased the stored Ca2+ to 42, 22, and 9%, respectively, of Ca2+ storage without halothane (P less than 0.001). However, hypertrophied muscle demonstrated slightly less depression (P less than 0.05 by analysis of variance).(ABSTRACT TRUNCATED AT 250 WORDS)


Sexual differentiation and the germ cell in sex reversed gonads after aromatase inhibition in the chicken embryo. Chicken embryos were treated on day three of incubation with a steroidal or a non-steroidal aromatase inhibitor (1-methyl-androstendion, CGS 16949 A). Complete sex reversal of ovaries into testes or intermediate stages of sex reversal resulted from the inhibitory effect on oestradiol formation during gonadal development before and during sexual differentiation. Germ cell differentiation shifted from the female to the male pattern depending on the local advance of sex reversal.


Acute bronchodilator trials in chronic obstructive pulmonary disease. Short-term trials of bronchodilator drugs are widely used to assess patients with stable chronic obstructive pulmonary disease (COPD), but there is an uncertainty about the equivalence of the FEV1 response to beta-agonists and anticholinergic drugs, their relative ability to identify patients likely to improve with corticosteroids, the most appropriate way to express the results of these tests, and whether age or allergic status affects the beta-agonist and anticholinergic response differently. We studied 100 consecutive patients with stable COPD (mean FEV1, 0.96 +/- 0.48 L; mean age, 62 +/- 8 yr). Spirometry was measured before and after either 5 mg of nebulized salbutamol or 500 micrograms of nebulized ipratropium bromide and repeated after 2 wk of 30 mg of oral prednisolone daily. Total IgE, specific RAST, and skin prick testing values were recorded. Using modified American Thoracic Society response criteria, 33 patients failed to bronchodilate after the acute trials, 16 responded only to nebulized salbutamol, 17 to nebulized ipratropium, and 34 to both drugs. Twenty-two patients improved after corticosteroids. This was usually detected by a positive acute trial response (salbutamol 90% specific; ipratropium 84% specific). Baseline FEV1 differed between days, and in those who responded on only 1 day, this variation correlating with the response to ipratropium (r = 0.66). Expressing the response criterion as a percentage change in the available bronchodilatation increased the numbers responding with a high baseline FEV1, and vice versa. Neither age nor allergic status was related to the change in FEV1 after either drug in these patients. In COPD patients, testing with high-dose nebulized bronchodilators identifies a substantial number of partially reversible patients whatever age it is employed.(ABSTRACT TRUNCATED AT 250 WORDS)


[Pharmacokinetic studies of menogaril (TUT-7) with rats]. Menogaril (TUT-7) is a novel antitumor antibiotic belonging to anthracyclines. The pharmacokinetic parameters derived from plasma concentration-time profiles after repeated (for 14 days) or single oral administration of TUT-7 to rats were found to be not significantly different by either administration schedule. The rats with artificial liver dysfunction were obtained by subcutaneous application of carbon tetrachloride (CCl4, 1 ml/kg) for 3 days. After oral administration of TUT-7 to the rats with CCl4-induced liver toxicity (3 daily administrations of 1mg/kg, S.C.), the maximum plasma concentrations (Cmax) and AUC of both the unchanged drug and its metabolite N-Demethyl menogaril, were increased. Also over all elimination was slower in animals with liver dysfunction.


[Investigation of anti-emetic effect of ondansetron tablet in multiple doses on nausea and emesis associated with cisplatin]. The anti-emetic effects, safety and usefulness of ondansetron, a 5-HT3 receptor antagonist, given orally once daily for 3-5 consecutive days, were investigated in patients receiving a high single dose (greater than or equal to 50 mg/m2 or 75 mg/body) or lower multiple doses (greater than or equal to 15-20 mg/m2/day for 3-5 consecutive days) of cisplatin. Ondansetron 4 mg was administered orally once daily for 3-5 consecutive days. Efficacy rates in controlling nausea and emesis over the 3-5 days were 77.3% (17/22 cases) and 66.7% (6/9 cases) in patients receiving a high single dose and lower multiple doses of cisplatin, respectively. Side effects were observed in 2 cases (headache and elevation of blood pressure in one case and only headache in the other case.). Abnormality in clinical laboratory findings was observed in 1 case. From the above, ondansetron, showing high efficacy by oral administration 4 mg once daily for 3-5 consecutive days, without any problem in safety, was considered to be a useful anti-emetic agent.


[Examination of inhibitory effect, safety and usefulness of SN-307 (ondansetron) administered orally once daily for 3-5 consecutive days on nausea and emesis associated with non-platinum anti-cancer drugs]. We examined the anti-emetic effect, safety and usefulness of ondansetron hydrochloride, a selective 5-HT3 receptor antagonist, given orally once daily at the dosage of 4 mg, for 3 to 5 consecutive days to patients with nausea and emesis induced by non-platinum anti-cancer drugs such as cyclophosphamide, doxorubicin and carboplatin. Out of 84 cases where anti-emetic effects were evaluated, numbers of cases assessed as excellent and good were 36 (83.3%) and 34 (40.5%), respectively, the efficacy rate being 83.3% (70/84). Side effects, such as moderate constipation (3 cases) and mild headache (3 cases), were observed in 8/85 cases (9.4%). Abnormalities in clinical laboratory findings including elevation of hepatic function and uricacid values and increase in eosinocyte counts, were observed in 3/85 cases (3.5%). As to overall safety, 78/85 cases (91.8%) were evaluated as having no problem in safety, and 7/85 cases (8.2%), as having minor problem in safety. As to clinical usefulness based on anti-emetic effect and overall safety, out of 79 cases the drug was assessed as very useful in 29 cases (36.7%) and useful in 35 cases (44.3%), the rate of "useful" or above being 81.0% (64/79). Furthermore, when ondansetron was administered in 3 courses of chemotherapy, though the number of patients was small, it was shown that anti-emetic effect of ondansetron did not decline and no problem in safety was observed. From the above, ondansetron which exerted adequate anti-emetic effect in 4 mg once daily doses was considered as a useful and safe anti-emetic in treatment of nausea and emesis associated with cancer chemotherapy.


[Evaluation of SN-307 (ondansetron), given intravenously for the treatment of nausea and vomiting caused by anticancer drugs including cisplatin-open study]. The anti-emetic effect, safety and clinical usefulness of ondansetron for the treatment of nausea and vomiting caused by anticancer drugs including cisplatin, was evaluated by a multi-institutional study in patients with various malignancies. In this study, ondansetron was given intravenously with mainly a single dose of 4 mg to intervene nausea and vomiting. 1. Efficacy ratio of overall effects on nausea and emesis observed for 24 hours after treatment was 69.8%. 2. No side effect was observed. Laboratory tests showed temporary elevation of serum uric acid level in 1 patient in the group given 4 mg. 3. From these results, it seems that ondansetron, given intravenously after initial vomiting, was highly safe and clinically useful anti-emetic for the treatment of nausea and vomiting associated with anti-cancer drugs.


[A case of inflammatory breast cancer treated with medroxyprogesterone acetate (MPA) in combination with intra-arterial infusion chemotherapy]. A 55-year-old female with severe inflammatory breast cancer was treated with the combined use of MPA and the intraarterial infusion chemotherapy. One cycle consisted of 4'-epi-adriamycin; 210 mg (day 1, 4 and 8) and daily administration of MPA; 1,200 mg. A marked shrinkage of the tumor was obtained with this treatment. The regressive change was noted not only in the primary lesion but in lymph nodes of the axillary region. Therefore, the combined use of MPA with intra-arterial infusion chemotherapy may well contribute to the treatment of inflammatory breast cancer.


Inocoterone and acne. The effect of a topical antiandrogen: results of a multicenter clinical trial. Because acne is androgen dependent, antiandrogen therapy might improve the condition. Inocoterone acetate (RU 882) is a nonsteroidal antiandrogen that binds to the androgen receptor and has antiandrogenic activity in animal models. To test its topical effect on acne, 126 male subjects with facial acne completed a 16-week, multi-center, double-blind study in which the twice-daily application of a 10% solution of inocoterone was compared with vehicle solution. Baseline and monthly examinations included acne lesion counts and general and endocrine laboratory tests. Inflammatory papules and pustules showed greater reduction in the inocoterone-treated subjects than in the subjects treated with vehicle. This difference achieved statistical significance by week 12 (24% reduction vs 10%) and week 16 (26% reduction vs 13%) and, with longitudinal analysis, throughout the course of the study. Global assessments and changes in comedo counts and sebum excretion rates were not significantly different between the groups. No serious adverse reactions were encountered. In this double-blind study of 126 male subjects with acne, a topical solution of the antiandrogen inocoterone, compared with vehicle, produced a modest but statistically significant reduction in the number of inflammatory acne lesions.


Coffee and coronary heart disease.

Coffee and coronary heart disease. We determined if coffee consumption is associated with an increased risk of developing coronary heart disease. Articles published between 1966 and August 1991 examining a possible link between coffee and coronary heart disease were identified by a computer-aided literature search (Medline) and by standard bibliographic searches. All prospective cohort studies providing data on daily coffee consumption and coronary events (acute myocardial infarction and/or coronary death) were included. Data from each published article were extracted. Additional unpublished data augmenting those published for one study were also included. Each cohort was categorized by reported daily coffee consumption. Incidence of coronary events at each level of coffee consumption was the primary outcome. Eleven prospective studies were included. The coronary events for subjects consuming little or no coffee (less than or equal to 1 cup per day) were compared with event rates for those consuming greater amounts of coffee. The studies exhibited heterogeneity of results. The typical odds ratios and 95% confidence intervals across studies were estimated by logistic regression analysis. Coffee intake from 1 to 4 cups per day was not associated with any increase in coronary heart disease occurrence compared with 1 cup or less per day (odds ratio, 1.01; confidence interval [0.93, 1.11]). The odds ratios for 4 to 6 and 6 cups or more per day compared with up to 1 cup per day were 1.01 (0.90, 1.12) and 1.09 (0.97, 1.22), respectively. There is no association between coffee consumption and the occurrence of coronary heart disease. This conclusion holds in the absence of adjustment for other coronary risk factors.


The diagnosis of disability. Treating and rating disability in a pain clinic. Medical diagnosis sanctions illness and directs physicians toward effective treatment. In chronic illness, these two functions of diagnosis can come into conflict. Nowhere is this conflict more striking than in the case of disability ratings for those with chronic pain. An institutional case study examining the relation between a pain clinic and a worker's compensation program is presented and analyzed in terms of two questions: (1) Is it ethical for one physician to both treat pain and rate disability in patients with chronic pain? (2) Is physician rating of disability due to pain scientifically valid? Ethical and conceptual analyses support a negative response to each of these questions. The roots of the ethical and scientific problems concerning disability ratings are identified in society's demand to differentiate medical and nonmedical distress. We propose a system of time-limited compensation for pain as a therapeutically superior alternative to disability ratings.


Clinical relevance of nighttime blood pressure and of daytime blood pressure variability. The purpose of this study was to assess whether hypertensive target organ damage is related to average nighttime blood pressure (BP) and to BP variability. Sixty-seven normotensive subjects and 171 borderline, 309 mild, 140 moderate, and 41 severe hypertensive patients were studied with noninvasive ambulatory BP monitoring. Each subject was assigned a target organ damage score of 0 to 5 on the basis of funduscopic changes and degree of left ventricular hypertrophy calculated from electrocardiogram and chest roentgenogram. When the 728 subjects were subdivided into five classes of increasing daytime BP, in each class a significantly higher degree of target organ damage was present in the subjects with higher nighttime diastolic BP. A similar, although nonsignificant, trend was observed in the subjects with higher nighttime systolic BP. In particular, higher nighttime BP levels were accompanied by a more severe degree of left ventricular hypertrophy. As for variability, subjects with higher daytime systolic BP SD, but not with higher daytime diastolic SD, displayed a more severe degree of target organ damage; this was accounted for by a higher degree of retinal abnormalities. The association between target organ damage and systolic BP SD was present both in men and women, while that with nighttime BP was present only in men. No relationship was found between degree of cardiovascular complications and peaks of pressure. These results suggest that a reduced day-night BP difference and an increased daytime BP variability, evaluated as the SD, are associated with a higher degree of hypertensive cardiovascular complications. Whether this BP profile is the cause or the consequence of target organ damage remains to be established.


Non-innervated Merkel cells and Merkel-neurite complexes in human oral mucosa revealed using antiserum to protein gene product 9.5. Merkel cells are non-keratinized cells present in many different epithelia, but whose origin and functional role are still controversial. They were here investigated by means of antisera to the neural and neuroendocrine markers protein gene product 9.5 (PGP 9.5), and neurone-specific enolase. The expression of both markers in Merkel cells of human gingival and palatal mucosa was confirmed. Merkel cell-neurite complexes and isolated non-innervated Merkel cells had a similar morphology when stained by either antiserum. Merkel-neurite complexes were clustered in relatively large numbers in the lingual gingiva, thus constituting structures closely similar to the 'touch domes' in the skin. Clusters of non-innervated cells showing the same immunohistochemical features as Merkel cells were also demonstrated. In other areas of the oral mucosa, the innervated and non-innervated elements were only occasionally seen but there were many encapsulated Meissner-like receptors. When comparing the two different antisera, anti-PGP 9.5 appeared to provide a more consistent labelling of small fibres inside the epithelium and of bulb-like terminals on Merkel cells.


Scissor dissection technique for laparoscopic cholecystectomy: an alternative to laser and electrocautery. A sharp dissection technique, using specially designed curved insulated scissors, is described for use in laparoscopic cholecystectomy. This technique is a suitable alternative to laser and electrocautery, and produced a significant shortening of operating time.


Diagnosis and surgical management of endometriomas. Fifty two patients with endometriomas greater than 1 cm were treated by surgical excision either with or without ovarian closure. Diagnosis is reliable when clinical features of the pain, vaginal ultrasound, and laparoscopy, including ovarian mobilization and needling, are considered. Fifty of 52 patients were free of pain after 1 year and 26 (50%) became pregnant within 1 year. A second laparoscopy is justified if pain persists or pregnancy does not occur. Adhesive disease was the most common complication (40%), and persistent or recurrent endometriosis occurred in 15%. Surgery by laparoscopy with drainage and excision of the endometrioma without ovarian sutures may be more effective than excision of the endometrioma and ovarian suture.


Human platelets express the SERCA2-b isoform of Ca(2+)-transport ATPase. Previous biochemical studies suggested that the human platelet Ca2+ATPase system may be cell-specific. To test this hypothesis, we first undertook the molecular cloning of Ca2+ATPase from human erythroleukaemia (HEL) cells, because this human cell line exhibits megakaryocytic features and expresses a Ca2+ATPase that cross-reacts with platelet Ca(2+)-ATPase. For this cloning, an HEL-cell cDNA library was screened with a rat cardiac Ca2+ATPase cDNA probe. The insert of the longest clone isolated was 3.9 kb and its sequence displayed a 100% identity with that of the non-muscle human Ca2+ATPase 2-b isoform, termed SERCA2-b (sarco-endoplasmic-reticulum Ca2+ATPase). The 3.9 kb cDNA covered a subtotal coding region and part of the 3' non-coding end of the SERCA2-b mRNA. It cross-hybridized with the 4 kb transcript species of cardiac SERCA2-a and with non-muscle SERCA2-b mRNAs, but not with fast-skeletal-muscle SERCA1 mRNA. We next confirmed that SERCA2-b was a component of the platelet Ca2+ATPase system because (1) the platelet clones isolated from a platelet cDNA library exhibited a 100% homology with HEL-cell cDNA; (2) SERCA2-b mRNA was amplified by PCR on total platelet RNA and (3) platelet Ca2+ATPase cross-reacted with a polyclonal SERCA2-b-specific antiserum. Platelets therefore contain a Ca2+ATPase definitely identified as the SERCA2-b isoform of Ca2+ATPase, thus eliminating the possibility that they only contain a single specific Ca2+ATPase.


A large decrease in heat-shock-induced proteolysis after tryptophan starvation leads to increased expression of phage lambda lysozyme cloned in Escherichia coli. The R gene coding for phage lambda lysozyme (lambda L), cloned under the control of the PL promoter on a multicopy vector, is expressed in an Escherichia coli strain auxotrophic for tryptophan. Induction by a thermal shift after tryptophan supplementation in a culture initially brought into stationary phase by tryptophan starvation leads to highly increased expression. A thermally unstable mutant protein, difficult to obtain under standard conditions, can be easily produced by post-stationary-phase expression. It is shown that this is due to a drastic decrease in the heat-shock-induced proteolysis normally observed on thermal induction. These data are discussed in relation to our present knowledge of stringent and heat-shock responses.


Isolation of human retinal genes: recoverin cDNA and gene. A human retina cDNA library enriched for retina-specific clones was prepared by subtraction with a non-retina population of cDNA in combination with polymerase chain reaction (PCR) amplifications. A highly retina-specific cDNA clone (1190 bp) was obtained through this library encoding a 200 amino acid protein with three calcium binding sites and 87% homology to the bovine photoreceptor protein, recoverin, which has been shown to mediate the recovery of the dark current after photoactivation, and 58% homology to the calcium-binding chick cone protein, visinin. Analysis of the gene indicated a 9-10 kb single-copy gene with at least three exons and two introns. The three exons contained the entire coding sequence, and all of the calcium-binding EF-hand regions were in putative exon 1. The recoverin gene was mapped to human chromosome 17 by hybridization to a panel of human-rodent hybrid DNAs.


[Incidence rates of cerebral palsy, severe mental and motor retardation, and Down syndrome in the city of Higashiyamato in suburban Tokyo]. We investigated the incidence rates of three neurological diseases in childhood in the City of Higashiyamato in suburban Tokyo with a total population of about 70,000. The number of liveborn babies during 1985-1989 was 3,958. The number of patients with cerebral palsy (CP) was 9 and the incidence rate was 2.2/1,000, which was equal to the reports from several countries. Four out of 9 patients with CP had mild motor handicaps and were expected to "outgrow" their handicaps. The number of patients with "severe mental and motor retardation" (SMMR) was 4 and the incidence rate was 1.0/1,000. Prenatal brain damage played a major role in the pathogenesis of CP and SMMR. The number of patients with Down syndrome (DS) was 7 and the incidence rate was 1.8/1,000. Incidence rates of CP, SMMR, and DS still remain high and further strategy to prevent pediatric neurological diseases is necessary.


[A clinical course and autopsy results of an 8-year-old severely handicapped girl with marked periventricular leukomalacia]. We reported a clinical course and autopsy results of an 8-year-old severely handicapped girl with marked periventricular leukomalacia. She was well until 3 days prior to first admission in local hospital. Two days prior to admission, she began to vomit. Twelve hours later, she was noted to be lethargic and developed malaise with frequent vomiting. At physical examination on admission, she had frequent fits and her posture was decerebrate rigidity. Consciousness disturbance continued for two weeks. Thereafter, she became severely handicapped with spastic quadriplegia, mental retardation and intractable epilepsy. She was transferred to our hospital one month later. We cared her totally and carefully with our rehabilitation staff, but during her course several rare happening occurred; she suffered from subdural hemorrhage due to hypocupremia and received an operation for the release of contracture of her hips. She died of acute cardio-respiratory failure at 8 years and 5 months of age. Her autopsy findings were characteristic of the damage to an immature brain during development; cactus formation of cerebellar cortex and periventricular leukomalacia.


[Laparoscopy in acute appendicitis].

[Laparoscopy in acute appendicitis]. Our experience shows that laparoscopy is an excellent diagnostic method in cases where acute appendicitis is suspected, but when the clinical picture and tests are equivocal. Laparoscopy can help diagnose other abdominal conditions mimicking acute appendicitis and, in addition, may be used to remove the appendix in most cases, with advantages over open surgery.


The same chemicals induce different neurotoxicity when administered in high doses for short term or low doses for long term to rats and dogs. Dose- and term-dependent differences in the location and nature of brain lesions induced in rats and dogs by 2,5-hexanedione (2,5-HD), misonidazole, clioquinol, and acrylamide are reported. Subchronic neuropathies ("distal axonopathy") were induced by low-dose administration of these neurotoxicants and at high doses, lesions caused by acute or subacute neurotoxicity were found in the central nervous system (CNS). In rats, 2,5-HD induced extracellular edema, nerve cell degeneration, and axonal degeneration in the cerebellar and vestibular nuclei. Similar lesions were observed in misonidazole-treated dogs and clioquinol induced nerve cell degeneration in the hippocampus and malacia in the piriform lobes of these animals. In rats, acrylamide induced degeneration of Purkinje cells. Although the mechanism(s) underlying the differential neurotoxicity of high and low doses of these neurotoxicants remains unclear, we suggest certain biochemical mechanisms, cytotoxic edema and excitotoxicity, as factors in the production of such lesions after high-dose treatment.


Circulating myosin light chain I levels after coronary reperfusion: a comparison with myocardial necrosis evaluated from single photon emission computed tomography with pyrophosphate. This study was performed to assess the influence of coronary reperfusion on the serial serum myosin light chain (LC)I levels and to evaluate the relationship between the peak LCI level and the infarct size calculated from single photon emission computed tomography (SPECT) with technetium-99m pyrophosphate (Tc-99m PYP) in 11 patients who underwent coronary reperfusion. Blood was drawn before reperfusion, immediately after reperfusion, and once a day for 14 days, to estimate the time course of serum LCI release. The infarct size estimated by Tc-99m PYP ranged from 7.3 to 62.4 ml. The LCI levels obtained before reperfusion were less than 2.5 ng/ml but those obtained immediately after reperfusion were much higher. The value ranged from 2.7 to 9.7 ng/ml and that expressed as a percentage of peak LCI (% peak LCI) ranged from 19 to 83%. Collateral circulation, reperfusion arrhythmia and the degree of residual stenosis had no influence upon the % peak LCI. The correlation between peak LCI levels and SPECT-determined infarct size was good, with a correlation of 0.76 (p less than 0.01, regression line by least squares method y = 3.31 + 1.53x). Early serum LCI might be influenced by coronary reperfusion but the peak LCI value reflected acute myocardial necrosis in patients who underwent coronary reperfusion.


Some physical properties of implant abutment luting cements. The dislodging force, the compressive strength at 24 hours, and the film thickness of four resin composite luting cements (UDA, UDA with fluoride, Panavia OP, and DenMat) and a conventional glass-ionomer cement (Shofu Type I) were compared. The axial force necessary to dislodge each cemented 0 degree abutment from an internally threaded Steri-Oss implant (n = 5) was then determined using a mechanical testing machine. UDA with fluoride appears to be a significantly stronger luting agent for abutment cementation than is either UDA or DenMat (P less than .05). DenMat resin composite cement exhibited the highest mean compressive strength whereas Panavia OP had the lowest value for film thickness.


The captopril renogram in percutaneous transluminal angioplasty of the renal arteries. Technetium-99m DTPA renograms were performed before and after angioplasty in a 63-year-old man with bilateral renal artery stenosis (RAS), hypertension, and renal insufficiency. Decreased isotope uptake after captopril by the right kidney assisted in the selection of the right renal artery for angioplasty. Post-angioplasty improvement in both blood pressure control and renal function was accompanied by an absence of effect of captopril on the isotope uptake by the right kidney. In bilateral RAS, the captopril renogram is a useful tool for selecting the site for angioplasty, for assessing the adequacy of the procedure, and for long-term follow-up.


Cardiovascular effects of the novel potassium channel opener bimakalim in conscious pigs after myocardial infarction: a comparative study with nicorandil. The benzopyran-derivative bimakalim is an ATP-dependent potassium channel activator that has been shown to be a potent arterial vasodilator in anesthetized pigs. In the present study we evaluated the cardiovascular profile of bimakalim in normal conscious animals and conscious animals with chronic left ventricular dysfunction and compared the results to those obtained with nicorandil. In normal conscious pigs, bimakalim (37.5-300 ng/kg/min, n = 6) and nicorandil (10-80 micrograms/kg/min, n = 8) increased cardiac output from 2.7 +/- 0.1 l/min to 3.8 +/- 0.2 l/min and from 2.7 +/- 0.1 l/min to 3.9 +/- 0.3 l/min (both p less than .05) due to increases in heart rate (up to 62 +/- 14% and 74 +/- 9%, respectively, both p less than .05). The mean arterial blood pressure decreased gradually from 104 +/- 4 mmHg to 91 +/- 5 mmHg with bimakalim and from 98 +/- 3 mmHg to 84 +/- 5 mmHg with nicorandil (both p less than .05), due to similar decreases in systemic vascular resistance. LVdP/dtmax also increased with both drugs (up to 48 +/- 11% and 69 +/- 7%, respectively, p less than .05), but left ventricular end-diastolic pressure remained unchanged with bimakalim, while it gradually decreased from 9 +/- 1 mmHg to 5 +/- 1 mmHg (p less than .05) with nicorandil. In pigs with a 3- to 4-week-old myocardial infarction, the vasodilator responses to bimakalim (n = 8) and nicorandil (n = 9) were not affected, but the increases in heart rate and LVdP/dtmax were attenuated compared to the effects in the normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of disopyramide on left ventricular diastolic function in patients with hypertrophic cardiomyopathy: comparison with diltiazem. Left ventricular diastolic function before and after the administration of disopyramide (100 mg) or diltiazem (30 mg) was assessed in 10 patients with nonobstructive type hypertrophic cardiomyopathy. Left ventricular diastolic function was assessed by Doppler echocardiography. The peak early (E) and late (A) diastolic flow velocities and E/A ratio (E/A) were measured. Three hours after the administration of disopyramide, blood pressure did not significantly change, but heart rate was decreased significantly (p less than 0.01). Disopyramide increased the E velocity and E/A ratio from 43.8 +/- 15.0 cm/sec to 51.3 +/- 16.1 cm/sec and from 0.71 +/- 0.20 to 1.00 +/- 0.24 (each p less than 0.01), respectively, and decreased the A velocity from 63.9 +/- 18.5 cm/sec to 52.1 +/- 14.9 cm/sec (p less than 0.01). Diltiazem increased the E velocity and E/A ratio from 42.8 +/- 12.5 cm/sec to 46.4 +/- 13.4 cm/sec (p less than 0.05) and from 0.74 +/- 0.21 to 0.96 +/- 0.28 (p less than 0.01), respectively, and decreased the A velocity from 60.6 +/- 16.4 cm/sec to 50.2 +/- 15.6 cm/sec (p less than 0.01). These results indicate that disopyramide improved left ventricular diastolic filling in hypertrophic cardiomyopathy, and its effect was similar to that of diltiazem.


Attenuation of myocardial reperfusion injury by sulfhydryl-containing angiotensin converting enzyme inhibitors. Recent studies have suggested the beneficial effects of angiotensin converting enzyme (ACE) inhibitors against myocardial ischemic-reperfusion injury. This study was designed to compare the cardioprotective effects of two sulfhydryl ACE inhibitors, captopril and zofenopril, with those of a nonsulfhydryl ACE inhibitor, fosinopril. The efficacy of these ACE inhibitors to scavenge oxygen radicals in vitro were also examined. Isolated rat hearts perfused by the Langendorff technique were preperfused in the presence or absence of ACE inhibitors (50 microns for 15 minutes, and the hearts were then subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion. Zofenopril and captopril, but not fosinopril, improved postischemic left ventricular functions and reduced myocardial cellular injury, as evidenced by improved recovery of the first derivative of left ventricular pressure development and reduced creatine kinase release compared with control (p less than .05). Coronary flow was significantly increased by captopril and zofenopril only. The same two drugs also inhibited the enhanced lipid peroxidation during reperfusion. Although significant differences were not noticed in the postischemic myocardial membrane phospholipid composition, captopril and zofenopril reduced nonesterified fatty acid contents, including palmitic, linoleic, oleic, and arachidonic acids. In vitro studies demonstrated that captopril and zofenopril were able to scavenge hydroxyl radicals. These results indicate that among three ACE inhibitors, two sulfhydryl-containing drugs, captopril and zofenopril, possess cardioprotective as well as free-radical scavenging abilities. Attenuation of phospholipid degradation and lipid peroxidation may be contributory to the protective effects observed in this study.


Response of a human megakaryocytic cell line to thrombin: increase in intracellular free calcium and mitogen release. The CHRF-288-11 cell line has been previously shown to exhibit properties consistent with a megakaryocytic origin. The response of these cells to thrombin has now been investigated. Thrombin treatment of CHRF-288-11 cells results in both an increase in intracellular free calcium levels and secretion of mitogenic activity and beta-thromboglobulin. Cell viability is not affected. The mitogenic activity released from the cells is due primarily to the presence of basic fibroblast growth factor. Immunohistochemical data indicate a packaging of basic fibroblast growth factor into granular structures. Trypsin and phorbol 12-myristate 13-acetate also initiate release of mitogenic activity from this cell line, whereas under non-stirred conditions collagen and ADP do not. Through measurements of intracellular calcium levels it was determined that thrombin pretreatment of cells ablates a further response to thrombin, but does not block an increase in intracellular calcium levels due to trypsin. This suggests that these two agonists may act through different mechanisms. The thrombin-induced release reaction is inhibited almost completely by the reagents hirudin and dipyridamole, and only partially by indomethacin. These data indicate that the CHRF-288-11 cell line should provide an excellent model system in which to study the packaging of factors into granules which undergo regulated release.


Detergent sensitivity of the tonoplast H(+)-ATPase and its purification from Beta vulgaris. Tonoplast membrane fractions were isolated from beetroot (Beta vulgaris) using a refined method of preparation which significantly improved the yield of active tonoplast H(+)-ATPase, and electron microscopy showed these fractions to be a preparation of small vesicles, of diameter 500 nm to 50 nm and a minor fraction consisting of mainly tubular membrane structures of diameter 5 nm and length up to 1 micron. The stability of the tonoplast H(+)-ATPase was assessed in the presence of many biological detergents, using a linked assay. The addition of detergent to tonoplast membranes generally led to an increase in ATPase activity, and activity was maintained in a wide range of both non-ionic and zwitterionic detergents. Using the non-ionic detergent dodecyl maltoside, the tonoplast H(+)-ATPase was partially purified using ion-exchange chromatography on an HPLC system. Very high rates of ATP hydrolysis were recorded in these fractions. The purified membranes behaved as expected in the presence of known activators and inhibitors. An unexpected observation, however, was that low concentrations of vanadate could significantly increase the rate of H(+)-ATPase activity.


Structural modeling of the human erythrocyte bisphosphoglycerate mutase. Using the crystallographic structure of yeast monophosphoglycerate mutase (MPGM) as a framework we constructed a three-dimensional model of the homologous human erythrocyte bisphosphoglycerate mutase (BPGM). The modeling procedure consisted of substituting 117 amino acid residues and positioning 19 C-terminal residues (unresolved in the X-ray structure) by empirical methods, followed by energy minimization. Among several differences in the active site region the most significant appears to be the replacement of Ser11 in MPGM by Gly in BPGM. The C-terminal segment, which contains mainly basic amino acids, lines the cavity of the active site. The seven amino acid residues, which have been shown to be essential for the three catalytic functions of the human BPGM, interact with the amino acids in the protein core, near the active site. In addition, a cluster of several positively charged residues, particularly arginines, has been identified at the entrance of the active site; this cluster may serve as a secondary binding site for polyanionic substrates or cofactors, as required by a two-binding-site model of the catalytic activities. This model is in agreement with recent studies of an inactive BPGM variant substituent at an Arg position situated in this positively charged cluster. The position of Cys20 in the model constructed suggests that this residue is responsible for inactivation of the enzyme by sulfhydryl reagents. Subunit interfaces have also been constructed for BPGM by analogy with MPGM and suggest that, in addition to the known dimerization of BPGM, tetramerization may occur under certain conditions.


Evaluation of intraventricular teicoplanin for the treatment of neurosurgical shunt infections. Seven patients with staphylococcal neurosurgical shunt infections were treated with intraventricular teicoplanin. Two infants received 5 mg/d, three patients received 20 mg/d, and two patients received 20 mg every other day. Six of these patients also received intravenous antibiotics. Three patients had infections caused by methicillin-susceptible Staphylococcus epidermidis, and one patient had an infection caused by methicillin-resistant S. epidermidis. Three patients were infected with Staphylococcus aureus (one with a methicillin-resistant strain and two with methicillin-susceptible strains). The mean duration of intraventricular therapy was 16 days. Sterilization of cerebrospinal fluid (CSF) was obtained after an average of 4.4 days. All patients were cured both clinically and microbiologically. No significant adverse effects were observed in any patients. Penetration of teicoplanin into the CSF after intravenous administration was poor. However, after intraventricular administration, high and prolonged peak and trough levels of teicoplanin were detected in the CSF. Bactericidal activity of the CSF was remarkable, exceeding the 1:8 dilution in the majority of the cases. The alternate-day schedule of intraventricular administration of teicoplanin was as effective as the once-daily regimen.


Piperacillin plus amikacin vs. piperacillin plus amikacin plus teicoplanin for empirical treatment of febrile episodes in neutropenic patients receiving quinolone prophylaxis. A prospective, randomized trial was initiated to evaluate the efficacy of two antibiotic regimens, differing in the agent included with activity against gram-positive bacteria, for the empirical treatment of febrile episodes in neutropenic patients with hematologic malignancies (group 1, piperacillin plus amikacin; group 2, piperacillin plus amikacin plus teicoplanin). After 72 hours of therapy, patients in group 1 who were still febrile were administered teicoplanin and those in group 2 were administered amphotericin B. A total of 158 evaluable episodes were observed within 8 months. The success rate was 50.6% in group 1 and 60% in group 2. The response rate among patients who did not respond to the original regimen increased to 86.7% with the addition of teicoplanin (group 1) and to 90% with the addition of amphotericin B (group 2). There were 86 unexplained febrile episodes and 56 documented episodes of bacteremia (34 caused by gram-positive organisms). Our results indicate that teicoplanin is safe, well tolerated, and effective for the treatment of documented episodes of gram-positive bacteremia and as an empirical agent. The inclusion of teicoplanin in the initial empirical regimen appears unnecessary if a combination of antibiotics active against gram-positive organisms is used, unless infections are due to oxacillin-resistant staphylococci.


Enterococcus species in urinary tract infection. Significant urinary isolates have been prospectively recorded since 1971. Enterococcus species, a common cause of nosocomial urinary tract infection, have been identified, and susceptibilities to a range of antibiotics have been determined. In addition, isolates in 1988 were tested for breakpoint susceptibility to vancomycin and teicoplanin. Despite changes in the hospitals covered, isolation of Enterococcus species rose steadily from 4% in 1971 to 12.6% in 1990 in hospital patients and from 2% to 5.6% in general-practice patients (P less than .01). All isolates of Enterococcus species were sensitive to ampicillin. Teicoplanin inhibited all 526 strains tested at a concentration of 2 micrograms/mL, but the same concentration of vancomycin inhibited only 370 (70%). The increased prevalence of enterococcal urinary tract infection is probably the result of increasing use of catheterization and broad-spectrum antibiotics. Glycopeptides reach high levels in the urine, and teicoplanin might be an alternative for the treatment of urinary tract infections due to enterococci.


Efficacy of teicoplanin for enterococcal infections: 63 cases and review. Sixty-three cases of monomicrobial enterococcal infections treated with teicoplanin in two open clinical studies in Europe from 1982 to 1989 are presented. Infections were documented as endocarditis (n = 18); septicemia (n = 8); and urinary tract (n = 29), skin/soft-tissue (n = 6), or bone/joint (n = 2) infections. A total of 63 enterococcal strains were isolated; all of 29 strains tested were susceptible to teicoplanin (geometric mean MIC, 0.16 micrograms/mL; range, 0.06-0.5 micrograms/mL). Forty-eight patients were treated with teicoplanin alone and 15 were treated with teicoplanin in combination with an aminoglycoside. The rate of clinical cure was 84.1%; 4.8% of patients clinically improved, 7.9% had clinical recurrence, and 3.2% did not respond to therapy. Bacteriologic eradication was observed in 87.2% of patients; persistence, in 3.2%; recurrence, in 3.2%; and reinfection, in 4.8%. One case was not evaluable bacteriologically. Of 18 patients with endocarditis, 15 were cured with a mean daily dose of 5.4 mg/kg--six with monotherapy and nine with combination therapy. All patients with urinary tract infections were treated with monotherapy, and 89.7% were cured (mean daily dose, 4.6 mg/kg). Lower rates of clinical cure and bacteriologic eradication were observed in septicemic patients without endocarditis (62.5%). This study demonstrated a good efficacy of teicoplanin for the treatment of enterococcal infections due to susceptible strains, but further clinical studies would be useful for establishing optimal dosage and the indications for combination therapy, especially for severe infections.


Efficient photoaffinity labeling of human beta-hexosaminidase A. Synthesis and application of 3-azi-1-[(2-acetamido-2-deoxy-1-beta- D-glucopyranosyl)thio]- and -galactopyranosyl)thio]butane. Two photolabile thioglycosides (8 and 9) were synthesized by Koenigs-Knorr type glycosylation. These compounds, being enzyme-resistant analogues of N-acetylhexosaminides, were shown to be good competitive inhibitors of lysosomal beta-hexosaminidase (2-acetamido-2-deoxy- beta-D-hexoside acetamidodeoxyhexohydrolase, EC 3.2.1.52) action. For photoaffinity labeling 3H-labeled 8a was prepared by enzymatic oxidation with galactose oxidase followed by reduction with sodium [3H]borohydride. Compound 8a, when photolyzed in the presence of hexosaminidase, specifically labeled both subunits of the enzyme.


Tri-iodothyronine regulates survival and differentiation of rat cerebellar granule neurons. The effects of tri-iodothyronine (T3), which are known to affect cerebellar development, were tested on neuronal survival and differentiation of cultured cerebellar granule neurons. T3 in physiological concentrations increased both granule neuron survival after three days in culture and synaptic vesicle protein formation, as shown by immunostaining with antibodies against synaptophysin. Likewise, T3 increased the mRNA level for synapsin(I), but not that for GAP43 in granule neurons. Antibodies against microtubule associated protein Tau, which is expressed in developing neurites, showed that T3 also enhanced neurite formation.


Influence of target tissues on their innervation in old age: a transplantation study. Age-related changes in the nervous system might be intrinsic to the neurons or secondary to changes in the target tissues they supply. We have investigated this question by transplanting old and young vascular muscle into contact with young host nerves in oculo and observing the reinnervating nerve fibres. The density and pattern of reinnervation were those typical of the age of the target tissue, thus old transplants imposed an 'old' pattern of reinnervation on young host nerves. Our findings strongly support the hypothesis that target tissues determine the pattern and density of their innervation in old age.


Disruption of the SCL locus in T-lymphoid malignancies correlates with commitment to the T-cell receptor alpha beta lineage. The SCL/tal-1 gene on chromosome 1 is disrupted in up to 30% of immature T-cell malignancies, thus representing the most commonly recognized chromosomal abnormality in this disorder. Abnormalities of the gene occur rarely by chromosomal translocation into the T-cell receptor (TCR) delta locus and commonly by a site-specific 95-kb deletion, SIL-SCL (tald). Analysis of the SIL-SCL deletion by Southern blotting and polymerase chain reaction (PCR) in a series of 52 immature T-cell malignancies showed a type A deletion in 21% of cases, but no type B deletions. The type A deletion correlated with malignancies of the TCR alpha beta lineage, either on the basis of TCR alpha beta expression or bilateral TCR delta deletion. Fifty percent (5 of 10) of TCR alpha beta-expressing cells demonstrated the abnormality, whereas 0% (0 of 11) of TCR gamma delta-expressing cells did so. Six of eight SIL-SCL type A cases had undergone bilateral delta deletion, whereas only one of 31 cases with an apparently normal SCL gene had done so. These data demonstrate an association between SCL disruption and TCR alpha beta lineage differentiation and suggest that the SIL-SCL deletion occurs at the same stage of ontogeny as TCR delta deletion.


Unusual diffuse liver fibrosis accompanying transient myeloproliferative disorder in Down's syndrome: a report of four autopsy cases and proposal of a hypothesis. Transient myeloproliferative disorder (TMD), an acute leukemia-like disorder in neonates with Down's syndrome, is characterized by spontaneous regression of abnormal blast growth. Because proliferating blasts frequently express phenotypes of megakaryocytic lineage and, as a result, this disorder resembles acute megakaryoblastic leukemia (AMKL), it would be of interest to determine whether myelofibrosis, a common complication of AMKL, is also present in TMD. Pathologic observations of four autopsy cases of TMD showed that myelofibrosis was not present in any of them, whereas intralobular diffuse liver fibrosis was present in all of them. Laboratory data of four additional cases showed hepatic dysfunction in all of them, suggesting a close association between hepatic lesions and TMD. From these results, we propose a hypothesis that the abnormal blasts with megakaryocytic properties in TMD originate from the fetal liver and cause liver fibrosis, as AMKL cells are thought to cause myelofibrosis by producing collagen-stimulating cytokines in the bone marrow. This hypothesis also seems to explain some other unique aspects of TMD.


Lecithin cholesterol acyltransferase in human cerebrospinal fluid: reduced level in patients with multiple sclerosis and evidence of direct synthesis in the brain. Several studies suggest that apolipoproteins and the low-density lipoprotein receptor are implicated in lipid transport in the brain. Given that cerebrospinal fluid has been reported to contain cholesteryl esterifying enzyme, and that lipid metabolism in the brain is abnormal in subjects with multiple sclerosis, we examined the cerebrospinal fluid from eight control subjects with a normal cerebrospinal fluid IgG index, and without active demyelinating disease, and from eight subjects (6 were diagnosed as having multiple sclerosis) with an increased IgG index and the presence of oligoclonal banding in the cerebrospinal fluid, for the presence of the enzyme lecithin cholesterol acyltransferase and apolipoprotein(a). None of the subjects demonstrated impairment of their blood-cerebrospinal fluid barrier, as estimated by the cerebrospinal fluid/serum quotient of albumin. Lecithin cholesterol acyltransferase was detected in the cerebrospinal fluid of all control subjects, being 0.12 +/- 0.06 microgram/ml (mean +/- SD) or about 2.2% of that in serum (5.4 +/- 1.4 micrograms/ml). The cerebrospinal fluid lecithin cholesterol acyltransferase index was 5.2 +/- 2.5, very similar to the cerebrospinal fluid index of apolipoprotein E, a protein known to be synthesized in the brain. Since lecithin cholesterol acyltransferase mRNA is also expressed in the brain, we can conclude that the protein is synthesized and secreted in the brain. The cerebrospinal fluid concentration of lecithin cholesterol acyltransferase in the subjects with active demyelinating disease or multiple sclerosis was only about one-half of that found in control subjects (0.06 +/- 0.02 microgram/ml).(ABSTRACT TRUNCATED AT 250 WORDS)


Automated measurement of lipoprotein(a) by immunoturbidimetric analysis. Immunoturbidimetric analysis of lipoprotein(a) in plasma or serum was developed for use on the Roche COBAS FARA II and COBAS MIRA clinical chemistry analyzers. The components of the assay are: (1) buffer consisting of 2.25% polyethylene glycol in phosphate-buffered saline, 0.2% gelatin, and a surfactant; (2) fractionated goat anti-human lipoprotein(a) IgG; (3) five standards with lipoprotein(a) concentrations ranging from 0.05 to 1.0 g/l; (4) two controls with concentrations of approximately 0.2 and 0.5 g/l. The analyzer delivers sample and buffer, incubates the reaction mixture at 37 degrees C for 5 min, delivers neat lipoprotein(a) antibody, and incubates for an additional 10 min. The lipoprotein(a) concentration of samples is calculated by the COBAS DENS (Data Evaluation for Non-linear Standard Curves) option by fitting the standard curve values to a four-parameter logit-log curve model. Total imprecision results (CV%) for the FARA II and MIRA were under 11% (NCCLS protocol EP5-T). The assay is linear beyond the highest calibrator to 2.6 g/l. No interference was observed for plasminogen up to 2.3 g/l, apolipoprotein B up to 4.36 g/l, hemoglobin up to 10 g/l, bilirubin up to 4.0 g/l, and triglycerides up to 4.36 g/l. Comparison with a double monoclonal ELISA used at the Northwest Lipid Research Laboratories yielded: R = 0.970, slope = 1.013, and y-intercept = 0.00009 (n = 37). Comparison with a commercially available ELISA kit for lipoprotein(a) yielded: r = 0.987, slope = 1.243, and y-intercept = 0.024 (n = 40). This assay provides rapid, accurate, and precise screening of lipoprotein(a) in serum or plasma.


Update on technology assessment in dentistry. This review focuses on evaluations of particular clinical problems or technologies in dentistry that have used the recently developed technology assessment techniques of decision analysis, meta-analysis, and cost-effectiveness analysis. It also discusses general methodologic and implementation issues in the assessment of health-care technologies.


Categories, classes and criteria in childhood disability--experience from a survey in Jamaica. This paper reports a new classification and criteria for disabilities and handicaps used in a survey of childhood disability in Jamaica. Part of the International Classification of Impairments, Disabilities and Handicaps was used, with an alternative classification for disabilities similar to that of impairment, and with a complete set of criteria for levels of severity. For handicaps, the set proposed in the WHO manual, Training Disabled People in the Community, was used. No difficulties were encountered in the use of definitions or severity criteria. The inter-rater reliability for disability as a whole by community workers was 79% (kappa statistic 0.58), and for the physician and psychologist 90 and 100%. The handicap classification was easy to use but there was some confusion with resulting poor inter-rater reliability for some questions. This could be corrected by clarification of the meaning of the questions during training. We recommend use of this classification and criteria as being simple and realistic for surveys of childhood disability conducted by community workers.


Anthropometry, spinal canal width, and flexibility of the spine and hamstring muscles in 45-55-year-old men with and without low back pain. One hundred fifty 45-55-year-old men were divided into three groups: those with healthy backs, recurrent low back pain (LBP), and chronic LBP. These groups were studied with respect to anthropometry, spinal canal width, spinal sagittal configuration and flexibility, and the flexibility of the hamstrings musculature with straight leg raising (SLR). There were no differences between the groups with respect to anthropometry. The group with healthy backs had significantly greater lordosis and sagittal flexibility than the other groups. The width of the spinal canal was correlated to body height. The SLR test showed significantly higher values in the group with healthy backs and in the recurrent pain group than in the chronic pain group. The possible role of restoring normal range of motion to minimize the risk of LBP recurrence is discussed.


Assessing the function of functional assessment: a consumer perspective. The person who is most affected by the process of functional assessment is the consumer--the individual with a disability whose functional capacity is being assessed. Consumers want the functional assessment process to be conducted in a dignified manner and the results to be relevant to their needs. Many consumers, influenced by the independent living movement, focus primarily on their ability to live independently in their communities and on environmental barriers that prevent them from doing so. Yet, most functional status measures focus primarily on impairments and functional limitations, rather than on handicapping environmental factors. Consumers should be involved directly in the development and application of functional status measures so that these factors are considered appropriately. Such measures have important implications for defining programme eligibility, determining payment, assuring quality, and enhancing discharge planning.


Expert performance in low-back disorder recognition using patient pain drawings. Eight low-back-pain experts who regularly include pain drawings in their clinical workup were asked to classify 25 drawings. The experts used only the drawings to place cases into one of five broadly defined diagnostic categories: benign disorder, herniated disc, spinal stenosis, underlying disorder, or psychogenic disturbance. The physicians demonstrated adequate accuracy--51% correct--when compared with change (20% correct). Classification accuracy was greatest for psychogenic disorders (85%), followed by spinal stenosis (58%), herniated discs (52%), and benign disorders (50%). Predictions were comparatively poor for the underlying disorder category (10%). The individual physician accuracies varied from 44 to 60%. "Classic" pain patterns for each disorder group were identified by determining which drawings were correctly classified by most physicians. Physicians may wish to impart greater significance to pain drawings close to one of our "classic" patterns than to others.


Effects of lumbar belts on trunk muscle strength and endurance: a follow-up study of construction workers. The effects on maximal isometric trunk muscle strength and endurance after wearing a soft heat-retaining lumbar belt or a weightlifter's belt were studied. The soft belt (SB) study group comprised 12 construction workers with healthy backs, and the weightlifter's belt (WB) group comprised 24 construction workers with current or previous low back pain. The strength and endurance measurements were performed before the start of belt use, and after 1 and 2 months. The SB group increased the trunk flexor strength by 13% (p less than or equal to 0.01) after 2 months. The WB group increased the trunk flexor strength and endurance by 12% and 29%, respectively (p less than or equal to 0.001). No significant decrease of trunk muscle strength and endurance was found at the end of the follow-up period.


The role of prior knowledge on back-pain education. To investigate the effectiveness of the Geneva Back School (BS), we studied certain aspects of the retention of what was taught and the changes it induced in the patients. Thirty-nine BS patients were asked to draw their backs both before and after the BS. They were also asked to define the terms arthrosis and herniated disc once before the BS and twice after the program. Analysis of 78 drawings showed that the representation of the back was far from anatomical reality in both instances. The definitions of terms correlated poorly between patients and health care professional before BS. Teaching increased patient knowledge, but did not delete patients' prior notions. Our findings indicate that teaching strategies need to take into account patients' beliefs and knowledge. Health care professionals involved in BS programs should also be aware of the possible misunderstanding of medical terms. These factors may explain, at least partially, BS failures.


Segmental fixation of lumbar burst fractures with Cotrel-Dubousset instrumentation. A retrospective review of 17 patients who underwent bilateral transpedicular decompression, instrumentation with a Cotrel-Dubousset construct, and posterolateral fusion with iliac crest bone graft for treatment of lumbar burst fracture is presented. All patients were followed to fusion with an average follow-up of 18.9 months. Fifteen of sixteen patients returned to preinjury occupation and/or activity. All patients reported good to excellent clinical results. The average postoperative progression of kyphosis was 11.9 degrees. There was no significant change in anterior vertebral height between the preoperative and postoperative periods. We conclude that although excellent early clinical results can be obtained using this operative strategy, the long-term effect of residual kyphosis at the fracture site is unknown.


[Survival in esophageal cancer in high altitude]. Records of 5474 esophageal cancer patients treated in 1959-1983 have been analyzed. The patients came from various climatic and geographical zones of the high-mountain region. A correlation has been found between the survival of the patients, scope of the disease-oriented aid and hypoxia of high mountains. Total cumulative values are presented for survival of esophageal cancer patients by five-year intervals in various medico-geographical zones of high mountains and according to methods of treatment.


Phenotypic analysis of the chicken thymic microenvironment during ontogenic development. The development of monoclonal antibodies (mAb) reactive with the thymic microenvironment has identified distinct subpopulations within the stromal component, but the function of these subregions in intrathymic T-cell differentiation remains essentially an enigma. In this study, we have used such a panel of mAb to examine the chicken thymus during ontogenic development to gain insight into the contributions of these thymic regions to the distinct phases of T-cell development and to further characterize the development of this organ. Our reagents have demonstrated the complex differentiation of the primitive endodermal epithelium into more specialized structures and the development of other thymic stromal components from mesectodermal cells. We also describe molecules localized to the subcapsular and perivascular regions, which have an ontogenic expression corresponding to the early localization and stimulation of thymic precursors and another molecule on the medullary vasculature expressed corresponding to the exit of mature cells from the thymus. In addition, two markers of distinct medullary epithelial clusters are initially expressed corresponding to the appearance of T-cell receptor-1 (TcR-1) and TcR-2 positive cells in the medulla, respectively. These mAb potentially represent excellent reagents for further definition of the thymic modulation of T-cell differentiation.


Phenotypic characterization of chicken thymic stromal elements. Phenotypic profiles of the thymic stromal components provide an excellent approach to elucidating the nature of the microenvironment of this organ. To address this issue in chickens, we have produced an extensive panel of 18 mAb to the thymic stroma. These mAb have been extensively characterized with respect to their phenotypic specificities and reveal that the stromal cells are equally as complex as the T cells whose maturation they direct. They further demonstrate that, in comparison to the mammalian thymus, there is a remarkable degree of conservation in thymic architecture between phylogenetically diverse species. Eleven mAb reacted with thymic epithelial cells: MUI-73 was panepithelium, MUI-54 stained all cortical and medullary epithelium but only a minority of the subcapsule, MUI-52 was specific for isolated stellate cortical epithelial cells, MUI-62, -69, and -71 were specific for the medulla (including Hassall's corpuscle-like structures), MUI-51, -53, -70, and -75 reacted only with the type-1 epithelium, or discrete regions therein, lining the subcapsular and perivascular regions and MUI-58 demonstrated the antigenic similarity between the subcapsule and the medulla. Seven other mAb identified distinct isolated stromal cells throughout the cortex and medulla. Large thymocyte-rich regions, which often spanned from the outer cortex to medulla, lacked epithelial cells. These mAb should prove invaluable for determining the functional significance of thymic stromal-cell subsets to thymopoiesis.


Blocking NMDA receptors or nitric oxide production disrupts light transmission to the suprachiasmatic nucleus. Retinal stimulation with a brief pulse of light (200 lx, 3 min) stimulated heart rate in dark-adapted urethane-anaesthetized rats. This effect was inhibited by prior infusion of a competitive blocker of N-methyl-D-aspartate (NMDA) receptors, (+-)-3-(2-carboxypiperazin-4-yl)-propyl-L-phosphonic acid (CPP, 20 nmol) into the hypothalamic suprachiasmatic nucleus (SCN) region. Furthermore, this inhibition of the stimulatory effect of light on heart rate was mimicked by prior infusion in the SCN region of a competitive blocker of nitric oxide (NO) production from L-arginine, NG-nitro-L-arginine methyl ester (40 nmol), or a blocker of the soluble guanylate cyclase. Methylene blue (20 nmol). None of these effects was seen when infusions were made in a region located 2 mm dorsal to the SCN or when a non-visual stimulus (tail pinch) was used to stimulate heart rate. These results point to a functional link between activation of an NMDA receptor coupled NO/cGMP signalling pathway and light transmission to the SCN.


Arcaine and magnesium inhibition of the NMDA receptor ionophore complex: evidence for distinct voltage-dependent sites. The inhibitory effects of the polyamine antagonist, arcaine, and magnesium on N-methyl-D-aspartate (NMDA) induced hippocampal [3H]norepinephrine release and [piperidyl-3,4-3H(N)]-[N-1-(2- thienyl)cyclohexyl]-3,4-piperidine (TCP) binding were studied. We report that the inhibitory effect of arcaine and magnesium on NMDA-induced [3H]norepinephrine release is diminished by increasing the extracellular K+ concentration, presumably reflecting a voltage-dependent block for both. However, unlike MK-801, the block by arcaine shows no evidence of use dependence. Further, the IC50 value for magnesium inhibition of [piperidyl-3,4-3H(N)]TCP binding varies with the state of activation of the channel, being the lowest when the channel is maximally activated and the highest when the channel is least activated. On the other hand, the apparent affinity of arcaine is not significantly affected by the activation of the channel by glutamate and glycine, but is decreased by the polyamine agonist, spermidine. These data suggest that the polyamine antagonist binding site is distinct from either the phencyclidine/MK-801 site or the voltage-dependent channel site for magnesium. Nonetheless, these data suggest that the site must be located in a region of the NMDA receptor ionophore complex capable of sensing transmembrane potential.


Detection of canine homologs of human MYC, BCL2, IGH, and TCRB genes by Southern blot analysis. Subsets of non-Hodgkin's lymphoma in humans have been shown to involve activation of protooncogenes such as MYC and BCL2 resulting from chromosome translocation involving the IGH and TCR genes. Malignant lymphomas in the canine present histologic and clinical subsets similar to those in humans. To study the genetic nature of these lymphomas, we undertook this study to determine, by Southern blotting analysis, the extent of homology between the human and canine genes MYC, BCL2, IGH, and TCRB using human gene probes. Our results, presented here, show that the organization of these genes in the two species is very similar.


A role for IgE in extrinsic allergic alveolitis? Receptors for the Fc portion of immunoglobulin E (IgE; CD23) can be detected on the surface of alveolar macrophages (AM) in extrinsic allergic alveolitis (EAA), using monoclonal antibodies in immunocytology. More than 50% of AM were positive in 16 of the 20 patients reported here, while the remaining 4 had 11-47% positive cells. Staining with anti-IgE antibody can, in addition, demonstrate endogenous IgE bound to the AM. This suggests that IgE might be involved in the process. Since IgE-mediated asthma is associated with bronchoconstriction, we asked whether EAA patients do in fact exhibit an obstructive component. In 3 out of 10 patients we did indeed find clearly increased airway resistance (greater than 30 kPa x s x l-1). These findings are consistent with the observation of immediate bronchoconstriction observed in some patients upon allergen challenge. Since only 1 of the 20 patients studied was a smoker, and since in the literature the majority of reported cases of EAA are in nonsmokers, we speculate that smoking may interfere with immunological processes leading to EAA.


Dopamine D1 and D2 antagonists block L-dopa-elicited air-stepping in neonatal rats. When administered to rat pups that have been suspended in air, L-3,4-dihydroxyphenylalanine (L-DOPA) induces a highly stereotypic locomotor response referred to as air-stepping. In order to determine the respective roles of dopamine D1 and D2 receptors in the expression of air-stepping, the abilities of the selective D1 antagonist SCH 23390 and the selective D2 antagonist spiperone to block L-DOPA-induced air-stepping in 5-day-old rat pups were assessed. Both antagonists increased latency to onset, and both decreased total duration of air-stepping by decreasing the number and length of air-stepping episodes. Neither SCH 23390 nor spiperone altered the topography of the air-stepping response; however, subjects receiving lower doses of spiperone spent significantly more time with the body dorsiflexed and limbs extended (extension/tremor activity) than did control subjects. The results suggest that both the D1 and D2 receptor subtypes are involved in the production of L-DOPA-induced locomotor activity.


Percutaneous techniques for the management of symptomatic gallbladder stones. Several non-operative treatments for the management of patients with symptomatic gallstones have been developed with the purpose of avoiding the considerable morbidity associated with open cholecystectomy. Minimally invasive techniques utilizing direct percutaneous puncture of the gallbladder are being increasingly used for the diagnosis and treatment of gallbladder disease and are the subject of this review. With the emergence of laparoscopic cholecystectomy the role of these techniques is less certain but they are likely to continue to be important in the management of high risk, elderly or medically unfit patients.


Atrial and brain natriuretic peptides: secretion during exercise in patients with essential hypertension and modulation by acute angiotensin-converting enzyme inhibition. 1. This study examined whether brain and atrial natriuretic peptides (BNP, ANP) are secreted together through the coronary sinus from the heart, and whether plasma concentrations of BNP and ANP were affected by ergometric exercise in patients with essential hypertension. The effects of temocapril, a potent angiotensin-converting enzyme (ACE) inhibitor, on plasma concentrations of these peptides was also examined. 2. The plasma concentrations of immunoreactive (ir) BNP and ir-ANP in the coronary sinus in seven patients with ischaemic heart disease during cardiac catheterization were far greater than values with plasma obtained at the same time from the femoral artery. 3. The plasma concentrations of ir-BNP and ir-ANP increased with exercise and were correlated with each other. Temocapril reduced the blood pressure and slightly (but significantly) decreased the levels of both peptides at rest and during exercise. 4. The results suggest that BNP and ANP were secreted together through the coronary sinus from the heart. The secretion was increased by exercise and suppressed by acute ACE inhibition. The increase in these peptides during exercise may reflect a compensatory mechanism against further elevation of blood pressure.


Inappropriately elevated levels of atrial natriuretic peptide may contribute to the pathophysiology of orthostatic hypotension. 1. Overnight recumbent and upright plasma atrial natriuretic peptide (ANP) levels were markedly elevated (P less than 0.001) in patients with orthostatic hypotension (OH). 2. Overnight urinary clearance of ANP was significantly lower (P less than 0.01) in patients with OH, and was inversely correlated with plasma ANP levels (r = -0.94, P less than 0.01). The same negative correlation (r = -0.87, P less than 0.01) was seen in normal subjects. 3. Reduced urinary clearance of ANP may be associated with reduced filtered load and increased binding of ANP to the neutral endopeptidase 24.11 receptor binding sites in the proximal renal tubule. 4. ANP may be involved in the pathophysiology of orthostatic hypotension.


Subpressor calcium infusion increases isovolumic left ventricular relaxation time and atrial natriuretic peptide in humans. 1. Subpressor calcium infusion for 1 h, which raised calcium levels to the upper limit of normal in normal subjects, increased plasma and urinary levels of atrial natriuretic peptide (ANP). 2. Heart rate fell, presumably due to carotid baroreflex stimulation (supported by the fall in noradrenaline) and the resultant fall in cardiac output prevented the expected rise in blood pressure due to the rise in total peripheral resistance (TPR). Thus the increase in ANP was not explained by an increase in blood pressure or noradrenaline. 3. There was no evidence for increased atrial stretch (no increase in atrial area or early velocity of left ventricular filling) as a mechanism for increased ANP. 4. Isovolumic left ventricular relaxation time increased, early velocity of ventricular filling decreased and TPR increased, consistent with increased tone in left ventricular and arteriolar muscle. 5. This suggests a direct effect of calcium on the atrial myocyte, stimulating ANP either through contractile or secretory mechanisms.


Prostaglandins and systolic blood pressure, but not angiotensin II, independently affect atrial natriuretic peptide levels in man. 1. Two hours after a single dose of indomethacin (INDO), plasma renin activity (PRA) and atrial natriuretic peptide (ANP) levels decreased, which is consistent with an effect of lowering prostaglandins (PG). 2. After 48 h of INDO, PRA remained low but ANP had increased, which is consistent with the known effect of prostaglandin inhibitors to cause sodium retention, with a resulting volume expansion. 3. Infusions of angiotension II (AII), which raises diastolic blood pressure (BP) 20 mmHg or more, consistently raised ANP levels. The ANP response to AII infusion was reduced 48 h after INDO, which is consistent with an important role for PG in AII-stimulated ANP release. 4. After PG were blocked with INDO, the stimulating effect of AII on ANP at doses that increased diastolic BP less than 20 mmHg was insignificant, whereas before INDO it was significant. 5. In dose-response studies, INDO increased the systolic BP response but decreased the ANP response to AII, which is consistent with a direct effect of PG on ANP that is independent of systolic BP. 6. Prostaglandins and BP are important in the ANP response to AII infusion in normal subjects, but AII itself appears to have little direct effect on ANP.


Development and validation of echocardiographic methods for estimating left ventricular mass in rats. 1. The aim of this study was to develop non-invasive echocardiographic methods of measuring left ventricular mass (LVM) in rats, and to determine their usefulness in detecting left ventricular hypertrophy. 2. After initial studies to identify the optimum transducer and to ascertain the resolution limits of echocardiography, the repeatability of LVM estimates was studied. The average difference between two independent estimates in 86 male rats (average LVM = 674.7 mg) was 5.4 mg, and the standard deviation of the difference was 107.6 mg. 3. To determine agreement between direct and indirect methods, LVM was measured in 38 male rats by echocardiography and compared with direct measurement of the left ventricular weight at sacrifice. The mean difference between the two methods was 9.14 +/- 56.6 mg. The limits of agreement were from -122.4 to +104.1 mg. 4. Echocardiography was then used to measure LVM in eight male spontaneously hypertensive rats and eight male normotensive Donryu rats at 9 weeks of age. The mean LVM of SHR was 768.2 mg +/- 152.6, which was significantly (2P less than 0.001) greater than the LVM of DRY (435.4 mg +/- 32.2). 5. We conclude that echocardiography provides a non-invasive, repeatable and relatively accurate estimate of LVM in rats. The method is a potentially useful tool for studying the development or regression of cardiac hypertrophy in longitudinal experiments.


Long-term angiotensin II antagonism in spontaneously hypertensive rats: effects on blood pressure and cardiovascular amplifiers. 1. The angiotensin II type 1 receptor antagonist, losartan, prevented the development of hypertension in spontaneously hypertensive rats (SHR). 2. Losartan also prevented the development of left ventricular hypertrophy and vascular amplifier abnormalities. 3. Part of the hypotensive effect induced by long-term treatment with losartan persisted for a long time after the withdrawal of treatment. 4. The results support the hypothesis that angiotensin II contributes to the development of hypertension and cardiovascular hypertrophy in SHR.


Open-label study of the safety and efficacy of Fungoid tincture in patients with distal subungual onychomycosis of the toes. Onychomycosis is the most frequent cause of nail diseases. An open-label study has been conducted to evaluate the safety and efficacy of Fungoid Tincture, a topical antifungal agent approved by the Food and Drug Administration for the treatment of onychomycosis of the toes. Ten patients with culture-proven distal subungual onychomycosis were treated twice daily for twelve months with topical Fungoid Tincture. Another ten patients with the same condition were treated with the vehicle alone. At monthly intervals, the target nail was trimmed, the nail bed debrided, and global clinical assessment recorded. After twelve months of therapy, all patients applying Fungoid Tincture showed negative findings on fungal culture. The vehicle alone benefitted several patients, and may have antifungal activity. Adverse effects were minimal, with mild peeling occurring in seven patients and erythema noted in one.


Two directions of dopamine D1/D2 receptor interaction in studies of behavioural regulation: a finding generic to four new, selective dopamine D1 receptor antagonists. A range of new, chemically distinct D1 dopamine receptor antagonists, SCH 39166, NO 756, A-69024 and BW 737C, were studied for their effects on behavioural responses to the selective D2 agonist RU 24213. Each D1 antagonist not only blocked typical sniffing and locomotor responses to RU 24213 but also released atypical myoclonic jerking behaviour, while the selective D2 antagonist YM 09151 blocked these typical responses but did not release jerking. The rank order of effectiveness of these D1 antagonists to release such D2 agonist-induced jerking was similar to that of their selectivities as D1 antagonists; also, the action of BW 737C showed complete enantioselectivity, the inactivity of its R-antipode BW 736C paralleling enantioselective blockade of D1 but not D2 receptors. It appears that while tonic activity through D1 receptors is necessary for the expression of typical D2-stimulated behaviour, via well-known cooperative/synergistic D1:D2 interactions, D1 tone also normally inhibits, via oppositional D1:D2 interactions, the expression of atypical D2-stimulated behaviours such as jerking. Oppositional D1:D2 interactions are evident using all of the classes of selective D1 antagonist currently known, and appear to constitute another general mode of dopaminergic regulation.


Hydroxylamine-dependent inhibition of rhodopsin phosphorylation in the isolated retina. Hydroxylamine (NH2OH), a substance known to accelerate the decay of the metarhodopsin II bleaching intermediate of rhodopsin, was examined for its effect on the light-dependent phosphorylation of rhodopsin in the intact, isolated retina. Groups of ovine and bovine retinas that had been pre-incubated in darkness with 32P-inorganic phosphate were supplemented with NH2OH at final concentrations of up to 20 mM, then irradiated and further incubated in darkness. Rod outer segments isolated from the incubated retinas were subjected to SDS-PAGE; the gel was analysed for 32P (autoradiography) and protein (Coomassie staining), to determine the specific radioactivity (ratio of 32P and protein levels; '32P/opsin') of the opsin monomer band. Among retinas of a given experimental group, 32P/opsin declined with increasing concentration of added NH2OH. The relative value of 32P/opsin exhibited by controls (0 mM NH2OH) was halved in the presence of about 1-2 mM NH2OH, and was reduced by greater than or equal to 80% in the presence of 20 mM NH2OH. Supplementation of the retina with 20 mM NH2OH 1 min after irradiation caused relatively little reduction in 32P/opsin. The results indicate that the light-dependent phosphorylation of rhodopsin in situ is substantially inhibited by NH2OH at millimolar levels. The data are discussed in relation to previous electrophysiological studies that have examined rod dark adaptation in NH2OH-treated retinas.


Decreased docosahexaenoic acid levels in retina and pigment epithelium of frogs fed crickets. Whole retina, rod outer segments, and retinal pigment epithelium of frogs (Rana pipiens) fed crickets for more than 1 year had significantly lower levels of docosahexaenoic acid (22: 6n-3) than the same tissues of frogs fed crickets for less than 1 month. Decreases in 22:6n-3 levels in these tissues were compensated for by increases in the n-6 polyunsaturated fatty acids (PUFAs), primarily 22:5n-6. There were no changes in the levels of saturated, monoenoic, or dienoic acids. Analysis of diacyl phospholipid molecular species (PLMS) revealed decreases in both the 22:6(n-3)-containing dipolyenoic molecular species in phosphatidylethanolamine and phosphatidylserine, and the monopolyenoic molecular species in phosphatidylcholine. These PLMS were replaced by species containing 22:5n-6 or other n-6 PUFAs. Examination of fatty acid methyl esters of total lipids extracted from crickets revealed that less than 1 mol% fatty acids were of the n-3 family, while more than 30 mol% were of the n-6 family. Thus, frogs raised on an n-3-deficient diet have reduced levels of n-3 PUFA in their retinas, rod outer segments, and retinal pigment epithelium. Although such changes have been reported for mammals, this is the first report of the effects of n-3 deficiency on the lipids of amphibians.


The effect of growth hormone supplementation on in vitro fertilization outcome: a prospective randomized placebo-controlled double-blind study. To determine the effect of growth hormone (GH) supplementation to a long gonadotropin-releasing hormone agonist (GnRH-a)/human menopausal gonadotropin (hMG) treatment protocol, on ovarian response, embryo quality, and clinical outcome in in vitro fertilization (IVF). Growth hormone or placebo were administered in a prospective randomized double-blind manner. Forty-two normal ovulatory, women who were 38 years of age or less with mechanical factor infertility and a normal male factor were selected for this study. Gonadotropin-releasing hormone agonist, 0.5 mg/d, was initiated in the midluteal phase of the preceding cycle and continued until the day of human chorionic gonadotropin (hCG) administration. Ovulation induction with hMG was started 14 days after pituitary down regulation (17 beta-estradiol [E2] serum level less than 30 pg/mL). Growth hormone (12 IU/d) or placebo were administered on days 1, 3, 5, and 7 of hMG treatment. Breaking the code at the completion of the study revealed that 20 women received GH and 22 placebo. The age and duration of infertility did not differ between the two groups. Follicular phase duration, hMG ampules used, serum E2, and number of follicles (greater than or equal to 14 mm) on day of hCG as well as number of oocytes and embryos achieved were similar in both groups. Embryo morphology and rate of cleavage were also similar. Insulin-like growth factor-I (IGF-I) serum levels did not change after pituitary down regulation and increased significantly both after GH/hMG and placebo/hMG ovulation induction treatment. Clinical pregnancy rate (PR) per embryo transfer and implantation rate were 40% versus 32% and 17.9% versus 11.3% in the GH and placebo groups, respectively, and were not statistically different. In normo-ovulatory women undergoing ovulation induction for IVF, GH supplementation to hMG after GnRH-a pituitary down regulation does not seem to augment ovarian response or improve embryo quality. The effect of this regimen on actual PRs and implantation rates needs further clarification.


Effects of ethinyl estradiol on semen quality and various hormonal parameters in a eugonadal male. To determine the influence of estrogens on male fertility. A 36-year-old eugonadal male was subjected to two different regimens of treatment with ethinyl estradiol (EE2). Sperm quality, immunoreactive luteinizing hormone (LH) and follicle-stimulating Hormone (FSH), testosterone (T), estrone (E1), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), prolactin (PRL) and sex hormone-binding globulin were determined at intervals of 2 weeks for 315 days. A gender dysphoria clinic. A transsexual male nurse. It was hypothesized (and confirmed) that by comparing the effects of increasing and constant dose of EE2 on fertility parameters, differences in estrogen-sensitivity would show more clearly. Furthermore, this procedure served to find the minimal dose of EE2 for complete testicular suppression. Low doses of EE2 (20 micrograms/d) had no negative effect on sperm motility and density for a period of approximately 4 weeks, whereas high doses (60 micrograms/d) reduced motility already after a few days and led to a pronounced decrease in sperm density after 2 weeks. After discontinuation of therapy, motility normalized faster than sperm density. Under increasing doses of EE2 there was a constant decrease of FSH that occurred several weeks earlier than that of LH. Under constant dose of EE2 (60 micrograms/d) the decrease of LH was delayed (with respect to FSH) by only a few days. The decrease in T showed a stronger correlation with that of FSH than with that of LH. Volume and fructose content of the seminal fluid correlated with the decrease in T. Rebound effects were observed for FSH, LH, T, and fructose during the therapy-free interval. Ethinyl estradiol therapy had no influence on the serum concentrations of E1, E2, and PRL. Estrone was the dominant estrogen before and after therapy with EE2. Adrenal gland activity was markedly suppressed by EE2, as reflected by the decrease in DHEAS. The suppressive effect of EE2 on FSH and sperm motility was more pronounced and consistent than on LH and sperm density. The T decrease appears to be mainly caused by a direct effect of EE2 on the testes.


Laparoscopic treatment of symptomatic diaphragmatic endometriosis: a case report. Extreme caution and meticulous surgery are imperative when treating the surface of the diaphragm. This procedure should only be performed by an experienced laparoscopic surgeon after appropriate consultation with a cardiothoracic surgeon. Proper care, a thorough understanding of surrounding anatomic structures, and familiarity with laparoscopic instrumentation including the CO2 laser are required for the safe laser vaporization or excision of any peritoneal surface using hydrodissection (7).


Bicornuate nonfused rudimentary uterine horns with functioning endometria and complete cervical-vaginal agenesis: magnetic resonance diagnosis. A case is reported of a 16-year-old adolescent with cryptomenorrhea. The patient had a congenital anomaly of a bicornuate, nonfused, separate rudimentary blind uterine horns with functioning endometria, and complete cervical-vaginal agenesis. Ultrasound, laparoscopy, and minilaparotomy for unilateral salpingectomy failed to accurately identify the exact classification of the anomaly. Magnetic resonance imaging, however, accurately correlated with operative findings of exploratory laparotomy and McIndoe procedure.


Adhesive properties of modified glass-ionomer cements. The incorporation of water-soluble polymers and/or vinyl monomers into glass-ionomer cements can yield toughened "hybrid cement-composites". This study compared a commercial water-hardening glass-ionomer cement and seven experimental hybrids in their bonding to both dentin and Silar composite. The cements were sanded and phosphoric-acid-etched or left with an unaltered matrix-formed surface when adhesion to composite was tested. The seven hybrids included: 15% 2-hydroxyethyl methacrylate (HEMA) with appropriate initiators/activators, 29% HEMA, 27% HEMA + 0.5% polyacrylic acid (PAA), 0.5% PAA, 1.5% PAA, 2.5% polyvinyl alcohol, and 2.5% gelatin. Acceptable bond strengths to applied composite and to dentin were observed for most of the modified hybrid cements. There were higher bond strengths with composite when the hybrids were left unetched. Bonding of some unetched, HEMA-containing cements achieved bond strengths (29% HEMA, 10.09 MPa) significantly higher than those of the unmodified cement (4.92 MPa). Resin-modified cements may promote better bonding by improved interaction and compatibility with the resin component of the composite.


Modulus of resilience as predictor for clinical wear of restorative resins. Eight posterior restorative resins were tested with respect to flexural strength, modulus of elasticity, and modulus of resilience. The mechanical properties were correlated to the two-year results of clinical wear tests. Linear relationships were found between flexural strength and clinical wear and between modulus of resilience and clinical wear. It was concluded that modulus of resilience be used in research and quality control for the prediction of clinical wear.


The use of continuous fiber reinforcement in dentistry. Fiber-reinforced composite (FRC) formulations were developed to serve as structural components for various dental appliances such as prosthodontic frameworks, retainers and splints. Poly(ethylene terephthalate glycol) and poly(1,4-cyclohexylene dimethylene terephthalate glycol) reinforced with continuous S-2 glass fibers were pultruded into continuous lengths with small rectangular cross sections. The microstructure was evaluated with SEM and optical microscopy. Fiber content and flexure properties were measured and compared to previous results by other authors. The present FRC contained 43-45 volume % fiber, which compared favorably with the 5-15 volume % fiber reported by all earlier investigators of dental FRC. The present materials achieved 65% of the theoretically expected modulus, in contrast to the typical value of 40% calculated in the earlier reports. The flexural strength and modulus of the experimental FRC were approximately 565 MPa and 20 GPa, respectively. The present FRC can be formed into individualized devices, and free fibers need not be manipulated by the operator. The improved properties and handling justify further study of these FRC as structural dental materials.


Effects of histamine H2-receptor antagonists and a proton pump inhibitor on the mucosal hydroxyproline content of ethanol-HCl-induced gastric lesions in rats. We evaluated the effects of different antisecretory agents (H2-receptor antagonists and a proton pump inhibitor) on collagen regeneration in rat gastric lesions induced by intragastric administration of 50% ethanol +0.15 N HCl (EtOH-HCl). The lesion indices showed the highest value 30 min after administration of EtOH-HCl and a significantly decreased value 15 h later. The mucosal hydroxyproline concentration was significantly increased 30 min after EtOH-HCl administration, reached a maximum 6 h later and subsequently decreased as time passed. Intraperitoneal administration of cimetidine at a dose of 100 mg/kg or famotidine at a dose of 5 mg/kg 30 min after EtOH-HCl administration could not reduce the lesion indices in less than 24 h and suppressed the increase in mucosal hydroxyproline concentrations significantly compared with the control group. On the other hand, treatment with 10 mg/kg of E-3810, a proton pump inhibitor, had no effects on the lesion healing nor on the fluctuation of mucosal hydroxyproline concentrations. These facts suggest that H2-receptor antagonists might delay the healing of EtOH-HCl-induced gastric lesions through the suppression of collagen regeneration under the condition of exclusion of gastric acid secretion.


Contrasting action of short- and long-term adrenaline infusion on dog skeletal muscle glucose metabolism. There are important differences between the short- and long-term effects of adrenaline on determinants of glucose tolerance. To assess this metabolic adaptation at tissue level, the present study examined the effect of acute and prolonged in vivo elevation of adrenaline on glycogen metabolism and glycolysis in skeletal muscle. Adrenaline (50 ng.kg-1.min-1) was infused for 2 h or 74 h and the results compared with 1 h 0.9% NaCl infusion in six trained dogs. Muscle glycogen content was reduced by long-term adrenaline (161 +/- 17 vs NaCl 250 +/- 24 mumol/g dry weight; p less than 0.05) but not short-term adrenaline (233 +/- 21) indicating a sustained effect of adrenaline on glycogen metabolism. Acutely, glycogen synthase I was reduced (short-term adrenaline 12 +/- 6 vs NaCl 22 +/- 7 mumol glycosyl units.g-1.min-1; p less than 0.05) but returned to normal with prolonged adrenaline infusion (20 +/- 5). In contrast, Km for glycogen phosphorylase alpha was not changed acutely (short-term adrenaline 31 +/- 6 vs NaCl 27 +/- 7 mmol/l inorganic phosphate) but was reduced during long-term infusion (19 +/- 4; p less than 0.05 vs short-term adrenaline). Thus, with short- and long-term adrenaline infusion, there were different enzyme changes, although likely to promote glycogenolysis in both cases. In the glycolytic pathway the substrates glucose 6-phosphate and fructose 6-phosphate did not change significantly and hexokinase was not inhibited. Acutely, phosphofructokinase had reduced Vmax (short-term adrenaline 34 +/- 6 vs NaCl 44 +/- 5 U/g; p less than 0.05) but was still above the maximal operating rate in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)