Prevalence and variance of temporomandibular dysfunction in orthognathic surgery patients. Seventy-five patients were studied retrospectively to assess the prevalence and variance of temporomandibular dysfunction in an orthognathic surgery population. Preoperatively, 49.3% of the sample presented with temporomandibular dysfunction. After orthognathic surgery, of the symptomatic patients, 89.1% had improved temporomandibular function after surgery, 2.7% were unchanged, and 8.1% had increased symptoms. Of the patients asymptomatic prior to surgery, 7.9% developed temporomandibular dysfunction postoperatively. Temporomandibular dysfunction was significantly more prevalent in patients with a Class II skeletal deformity than in those with a Class III deformity, and temporomandibular function generally improved in both groups postsurgically.


[Effect of coagulation inhibitor proteins (Calphobindins) on tissue factor expression of endothelial cells]. We established a method for measuring procoagulant action on human umbilical vein endothelial cells (HUVEC). HUVEC (2.5 x 10(4)/well) were stimulated with 1 microgram/ml endotoxin (lipopolysaccharide: LPS) for 6 hours at 37 degrees C in 5% CO2. After washing, the HUVEC were incubated with assay buffer containing Proplex ST 1 unit (factor VII)/ml, S2222 0.6 mg/ml and CaCl2 6.6 mM, for 30 minutes at 37 degrees C. The procoagulant activity was determined by measuring the supernatant at OD405. Calphobindin I, II and III (CPB I, CPB II and CPB III) are the calcium dependent phospholipid binding proteins that exhibit anticoagulant activity in vitro. In this study, we investigated the effects of CPB I, CPB II and CPB III on procoagulant activity (PCA) expressed on HUVEC. The results are as follows 1) CPBI inhibits the procoagulant activity on HUVEC in a dose-dependent manner (IC 50% less than 0.4 microM). The same doses (0.4 microM) of CPBII and CPBIII decreased the procoagulant activity to 28.1% (CPBII), and to 84.6% (CPB III). CPB anticoagulant activities were, CPBII greater than CPBI greater than CPBIII, in that order. 2) When 0.05% H2O2 was added to the cell culture medium wells, concentrations of CPBI in supernatants increased in a time-dependent manner, and they reached to the maximum after 8 hours. CPBI in supernatants after 24 hours were not detected without H2O2, but concentrations of 4.88 ng/ml/10(4) cells with 0.01% H2O2, and 9.60 ng/ml/10(4) cells with 0.05% H2O2 were detected.


[The study of DNA ploidy as a prognostic factor in uterine cervical cancer]. Nuclear DNA content was measured in 410 paraffin-embedded samples from 136 cases (43 stage Ib and 93 stage IIb) of uterine cervical cancer by flow cytometry, and the significance of DNA ploidy for use as a prognostic factor was evaluated. Positive parametrial invasion cases (p less than 0.05), metastasis to pelvic lymph nodes cases and lymphatic vessel permeation form (p less than 0.05) showed a high incidence of DNA aneuploidy. In the study of the relationship between DNA ploidy and prognosis by the Kaplan-Meier method, the DNA aneuploid group showed a tendency to a poor prognosis in all cases, large cell non-keratinizing cases (p less than 0.05), and large cell non-keratinizing pT2b with pelvic lymph nodes metastasis cases (p less than 0.05), and the DNA aneuploid group had significantly lower three- and five-year survival rates (p less than 0.05).


[Comparison of YAG and CO2 laser excisional conization for the treatment of uterine cervical neoplasia]. Thirty-nine patients with cervical neoplasia who were treated by CO2 laser excisional conization were compared with a group of 37 patients whose diagnosis and age were similar were treated by YAG laser excisional conization. Every operation in our series was performed on an outpatient basis. The differences between two groups were statistically significant: The CO2 laser group revealed the advantages in the healing periods from treatment to the end of epithelization (p less than 0.01: T test) and irradiation time (p less than 0.001). There was no difference in the blood loss during the operation. Both initial cure rates were 100% during the follow-up period of 21 to 65 months. During and post operations, more patients required additional measures such as sutures for uncontrollable bleeding in the CO2 laser group. In conclusion, both methods are felt to be good diagnostic and also therapeutic procedures for cervical neoplasia on an outpatient basis.


[Effect of endothelium-derived nitric oxide and prostaglandins on the endothelium-dependent vascular refractoriness to angiotensin II in pregnant rabbits]. Recently we demonstrated that the vascular response to angiotensin II (A-II) was attenuated in an endothelium-dependent manner by using the isolated ring specimen iliac arteries of pregnant rabbits. In this paper we investigated the possibility that three vasoactive substances, thromboxane A2(TXA2), prostacyclin (PGI2), and endothelium-derived nitric oxide (EDNO), might be involved in this refractoriness to A-II during pregnancy, by measuring the changes in the vascular response to A-II (pA2, intrinsic activity) of the isolated arterial rings of rabbits before and after the addition of an inhibitor specific for each of these three substances. Sodium ozagrel, TXA2 synthetase inhibitor, decreased the vascular response to A-II more in the blood vessels of pregnant rabbits, regardless of whether the endothelium was intact or denuded, than in the blood vessels of non pregnant rabbits. Tranylcypromine, a PGI2 synthetase inhibitor, significantly increased contractility in the blood vessels with intact endothelium of pregnant rabbits (i.a. = 1.39 +/- 0.099, n = 11, mean +/- SEM), compared to that in the blood vessels with intact endothelium of non pregnant rabbits (i.a. = 1.08 +/- 0.090, n = 7). Methylene blue, a guanylate cyclase inhibitor which blocks the effect of EDNO, amplified the vascular response in blood vessels with intact endothelium of both groups, and more intensely in the blood vessels of pregnant rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)


[Development of a fetal breathing movement tracking system using pulsed Doppler ultrasound]. Fetal breathing movements (FBM) form a useful means of monitoring fetal conditions and functional development. To develop a continuous and quantitative FBM monitoring system for clinical use, a non-imaging method using pulsed Doppler was devised. A pulsed Doppler cardiotocograph module was extended to obtain low frequency Doppler signals, by the addition of a 90 degree phase shifter, analog multipliers, quadrature detector, sample and hold circuits and low pass filters, to produce five simultaneous outputs representing movement at depths separated by 1.5cm intervals. These outputs represent the displacement inside tissue at the various depths. Signal processing was executed on a 32-bit computer with an A/D converter. On-line processing by means of a zero-crossing method and off-line arc tangent method with high accuracy displacement estimation were applied for calculation. With this system, FBM was detected as cyclic and regular displacements of a few hundred microns ranging from 0.5 to 1.5Hz. With digital signal processing of 2/3Hz high pass filtering, precise evaluation FBM was possible while rejecting gross movements due to maternal breathing, etc. Although further studies are required for clinical application, it appears that quantitative assessments of FBM should be possible with this technique.


[Mass-screening for ovarian cancer by means of transvaginal ultrasonography--study on size of ovary to select subjects requiring second screening]. Mass-screening for ovarian cancer by means of transvaginal ultrasonography has been performed in Aomori Prefecture since 1989. To select appropriate candidates to receive the second screening, the size of 44 normal ovaries removed by surgery and was measured studied on 10,692 ultrasonic pictures recorded on a VTR. The results were as follows: (1) All 44 ovaries were under 40mm. (2) In 3,806 (35.6%) of 10,692 women at the first screening, their ovaries were detected by ultrasonography. This detection rate was higher in young subjects and in the luteal and menstrual phases than in others. (3) Of these ovaries, 1,303 (34.2%) were under 19mm, 1,891 (49.7%) were 20-29mm and 614 (16.1%) were over 30mm in size. (4) The second screening was performed in 472 of the 614 women, and the size of the ovaries in 83 (17.6%) of them was under 29mm. (5) The frequency of ovarian size exceeding 40mm at the second screening, was 12.5% of the 30-39mm diameter group and 48.0% of the 40-49mm group at the first screening. There was no malignant tumor in the former, but there were one pre-malignant and one malignant tumor in the latter. These results indicate that the second screening should be performed for women having ovaries over 40mm in size.


[Usefulness of intraperitoneal carboplatin administration-- pharmacokinetic analysis]. A bolus of carboplatin (CBDCA) 200-450mg/body (148-292mg/m2) with 500ml saline was administrated into the abdominal cavity (ip) of 4 patients with ovarian cancer and 2 patients with uterine endometrial cancer, and concentrations of free and total platinum (Pt) in the blood and ascites were measured with the passage of time. Moreover, the results were analyzed with a 2-compartment model and moment analyses in order to study in vivo kinetics of CBDCA at the time of the ip administration. 1) The shift of Pt to blood through ip administration depended on the peritoneal clearance. Cmax in blood was seen one hour after ip in patients with a normal peritoneum, and was seen between 4 and 6 hours after ip in patients with peritonitis carcinomatosa. The level was lower in the latter group. 2) The non-binding rate of Pt with protein in the ascites at the time of the ip administration was correlated with the CBDCA concentration in the ascites. 3) The non-binding rate was 80% or more both in the ascites and in the blood within 4 hours after ip. The high level of the nonbinding rate appeared to cause prolongation of the presence of the free-Pt in the ascites and blood, especially in patients with peritonitis carcinomatosa. 4) AUC level in blood was equal to or higher than that observed when the same dose was administered iv. The levels of free-Pt and AUC in the abdominal cavity were 2 to 5 times higher than those in blood in patients with a normal peritoneum, and 7 to 14 times higher in patients with peritonitis carcinomatosa.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of D- and L-isomers of timolol on retinal and choroidal blood flow in ocular hypertensive rabbit eyes. An ocular hypertensive rabbit eye model was used to study the effect of L- and D-timolol on retinal and choroidal blood flow. Ocular hypertension was induced artificially by raising the intraocular pressure to 40 mmHg which reduced the ocular blood flow to 1/3 that of the normal blood flow. The effects of L- and D-isomers of timolol on the ocular blood flow of ocular hypertensive eyes were then determined using the colored microspheres technique over a range of 0-180 min after eyedrop instillation. It was found that L-timolol produced biphasic action on the blood flow in the iris, ciliary body and choroid by significantly reducing it initially at 30 min, then markedly increasing it later at 90 min and thereafter. Although L-timolol produced a tendency to reduce the blood flow in the retina, it was not statistically significant. At 90 min and thereafter, the blood flow in all ocular tissues was markedly increased by L-timolol. D-timolol did not reduce the blood flow of ocular tissues initially. There was a tendency to increase the blood flow in all ocular tissues from the very beginning by D-timolol. The increase of blood flow became significant at 90 min and thereafter, up to 3 hrs. D-timolol was less potent than L-timolol in increasing the blood flow in ocular tissues.


Effect of aldose reductase inhibitors on lenticular dulcitol level in galactose fed rats. We have shown that galactose cataract development is delayed or inhibited with the administration of aldose reductase inhibitors (ARIs). Dulcitol forms and accumulates in the lens of rats fed galactose. We undertook investigations to study the effectiveness of ARIs in preventing the formation and accumulation of dulcitol in the lens. Young Sprague Dawley rats were fed Purina Rat Chow with 50% galactose either with or without 15 mg sorbinil, 0.15, 0.5, or 1.0 mg E-0722/day/Kg body weight. At desired intervals following the initiation of diets, the lenses were processed for the determination of galactose and dulcitol levels. The lenticular dulcitol increased significantly in all animals fed galactose reaching a maximum level by approximately 15 days with comparatively lower levels in the groups fed ARIs with galactose; this increase was dose dependent in the groups fed E-0722. There was a subsequent, rapid drop in lenticular dulcitol by 18 days in all dietary groups. Interestingly, a second peak of increased lenticular dulcitol was observed in all groups. The correlation between dulcitol accumulation and cataract development is discussed.


Inhibition of ocular inflammation by chalcone derivatives and prednisolone. Posterior uveitis was induced by injection of 10 micrograms endotoxin intravitreally into rat eyes and anterior ocular inflammation was induced by injection of 0.75 mg of lens protein intracamerally into rabbit eyes. Four chalcone derivatives, RVC-556 (2'-hydroxychalcone), RVC-574 (2'-hydroxychalcone hydrazone), RVC-574P (2'-hydroxychalcone phenyl hydrazone) and RVC-588 (4,4'-dihydroxy chalcone) were studied along with prednisolone at a dose of 10 mg/kg i.p. t.i.d. for their anti-inflammatory actions. RVC-574 was more active than prednisolone in inhibiting posterior uveitis by 65% and 43%, respectively. RVC-556, RVC-574P, and RVC-588 did not affect the posterior uveitis in rats. On the other hand, anterior ocular inflammation was inhibited by 1% eyedrops of RVC-556, RVC-574P and RVC-588 but not by RVC-574. RVC-556 was more active than; RVC-574P was less active than; and RVC-588 was about equiactive as prednisolone in inhibiting anterior ocular inflammation by 77%, 47%, 69%, and 64%, respectively.


Influence of ion pairing salts on the transcorneal permeability of ionized sulfonamides. The effects of cationic ammonium, phosphonium, and arsonium ion pairing salts as well as anionic organic and inorganic salts on the transcorneal permeability of ionized sulfonamide carbonic anhydrase inhibitors have been studied in the excised rabbit cornea. Benzolamide, trichloromethazolamide (TCM), MK-927, and quaternary ammonium sulfonamide (QAS) were examined. The enhancement in the first-order rate constants (k(in)) for the first compound in the presence of pairing salts was as much as 15 times the basal rate, with smaller increases seen with the remaining three drugs. Ion pairing salts may represent a means for enhancing the transcorneal permeability of highly ionized drugs.


Ocular penetration of topically applied norfloxacin 0.3% in the rabbits and in humans. The kinetics of topically applied norfloxacin 0.3 percent were studied in rabbit and man. All measurements were performed by high-pressure liquid chromatography. Norfloxacin concentrations were investigated five to 120 minutes in rabbit ocular tissues after instillation of a single drop. In normal eyes, after 30 minutes, mean +/- SEM levels were 14.3 +/- 3.7 micrograms/g in cornea, 3.3 +/- 0.7 micrograms/g in conjunctiva, 0.2 +/- 0.1 microgram/g in aqueous humor. After removal of the corneal epithelium concentrations were as follows: 84.2 +/- 15.8 micrograms/g, 7.3 +/- 2.3 micrograms/g, 8.6 +/- 1.9 micrograms/g respectively. Penetration in posterior ocular tissues were rather poor. In human eyes, the intracorneal concentrations were assessed in patients being operated on corneal grafts. After instillation of 5 drops, the concentration in cornea was 15.5 +/- 2.1 micrograms/g. These data show that therapeutic levels of norfloxacin can be achieved in anterior ocular tissues, which may be of help in superficial infections of the eye.


Biopharmaceutical explanation for the topical activity of 6-hydroxyethoxy-2-benzothiazolesulfonamide in the rabbit eye. 6-Hydroxyethoxy-2-benzothiazolesulfonamide (compound 1), 6-hydrogen-2-benzothiazolesulfonamide (compound 2) and ethoxzolamide (compound 3) are carbonic anhydrase inhibitors, of which only compound 1 is active in lowering intraocular pressure when administered to the rabbit eye. They were compared for potency by inhibiting carbonic anhydrase I (CAase I) using the pH stat procedure. No differences were detected. Binding affinity and number of binding sites were identical; only a single binding site was operative. 14C-labelled compound 1 was used to measure the presence of an ocular metabolite which ranged from 17 to 57% in cornea, iris/ciliary body and aqueous humor. By maintaining drug solutions on either the corneal or conjunctival/scleral surfaces of the eye of anesthetized rabbits for 120 minutes, steady state concentrations of compounds 1-3 were determined in cornea, aqueous humor and iris/ciliary body. It was concluded that compound 1 penetrated both routes equally well and also accumulated at the active site in considerably higher concentrations than compounds 2 and 3. Compounds 2 and 3 did not accumulate in the iris/ciliary body nor did compound 3 penetrate the conjunctival/scleral route very well, approximately 5-20 fold lower than from the corneal route.


Lenticular uptake and distribution of xenobiotics and amino acids. The objective of this study was to explore the relationship between lipophilicity and the lenticular uptake of radiolabeled xenobiotics. The lenticular uptake of amino acids was also investigated. An organ-culture technique was employed and the partitioning of compounds into the rabbit lens was measured for compounds with log octanol/water partition coefficients (log P o/w) ranging from -1 to 7.3. Drug distribution in the lens was expressed as the concentration ratio of that in the lenticular section (capsule/epithelium, cortex, and nucleus) to that in the incubation medium, (C(lens) section/Cm). The drug partitioning into the lens capsule was facile for all of the compounds tested. The drug concentrations in the lens capsule were higher than those in the cortical and nuclear regions. For compounds with low partition coefficients (such as sulfacetamide and cimetidine), an apparent distribution equilibrium was achieved during a 5-hr period. The C(lens)/Cm value of polar compounds, being less than one, did not further increase by prolonging the incubation period. Only compounds with log Po/w values between 3 and 6 had Cnucleus/Cm values exceeding unity. The maximal values of Ccortex/Cm and Cnucleus/Cm, approximately 15 and 4, respectively, for anthracene (log Po/w = 4.5) and diethylstilbestrol (log Po/w = 5.1), were observed in this study. A bell-shaped relationship was observed between the lenticular uptake rate and drug lipophilicity, of which the maximum occurred around log Po/w of 4. These results indicate the existence of a lipophilicity window for favorable drug distribution into the deeper region of the lens. For several lipophilic compounds, such as padimate-O, values of Cnucleus/Cm increased steadily over a 24-hour incubation period. This suggests that the nucleus behaved as a deep compartment for these compounds. L-Cysteine and L-serine were actively taken up by the lens and the lenticular absorption of L-cysteine was concentration-dependent with Vmax and Km values of 18.3 mumol/gm/hr and 49.8 mM, respectively. In summary, a relationship between lenticular uptake and drug lipophilicity was demonstrated. The optimal log Po/w value for drug uptake into the lens was between 4 and 5. The slowness of reaching significant drug concentrations in the nucleus necessitates a chronic dosing regimen to deliver therapeutic drug levels inside the lens.


Eagle's syndrome: the Ochsner experience. Eagle fully described the syndrome that bears his name in 1948. He noted that the typical patient had undergone tonsillectomy in the past. Although reported in the literature, the carotid artery syndrome is frequently overlooked in patients manifesting craniofacial or pharyngeal pain but who have not undergone tonsillectomy. Cases representative of the variety of patients with Eagle's syndrome treated at the Ochsner Clinic Department of Otolaryngology are presented. The diversity of symptoms and its rather uncommon occurrence often make the diagnosis of Eagle's syndrome elusive. The anatomy and embryology of the stylohyoid complex is discussed, as well as the symptoms, differential diagnosis, workup, and treatment of Eagle's syndrome. We hope to refamiliarize the clinician with this condition in order that it be considered in the assessment of patients with craniofacial pain.


AIDS and multidrug-resistant tuberculosis: an epidemic transforms an old disease. Since 1985, tuberculosis case counts in the United States have increased, primarily because of the influence of the HIV epidemic. In addition, during this time outbreaks of multidrug-resistant tuberculosis among patients with AIDS or HIV infection have been reported in New York City and Florida. These outbreaks have occurred in hospitals and prisons and have been characterized by high case fatality rates, disease transmission within the institutions, and high infection rates in health care workers. The increase in tuberculosis rates and the outbreaks have raised concern that multidrug-resistant tuberculosis could become a widespread problem in the United States. Dealing with tuberculosis in the 1990s will require reconsideration of our current methods of tuberculosis prevention, diagnosis, treatment, and control.


Current concepts in the management and prevention of tuberculosis in adults. After a steady decline in incidence during most of this century, tuberculosis case rates stabilized in the mid-1980s, and since then have steadily increased. Several factors may have been responsible for the increase, including the influx of immigrants from endemic areas and the appearance of AIDS. This review outlines the current recommendations for treatment of tuberculosis in the otherwise normal patient, then discusses special problems which may affect treatment, including primary drug failure and relapse, pregnancy and lactation, extrapulmonary disease, AIDS, renal failure, and liver disease. The appearance and significance of multiple-drug-resistant tuberculosis (MDRT) in AIDS victims is discussed, and current recommendations for screening patients for the presence of tuberculosis are reviewed.


Attacking today's tuberculosis problem: a multifaceted, coordinated effort. Tuberculosis is making a comeback in communities across the nation. Increased rates of the disease, particularly with those having HIV/AIDS, have sounded the alarm that quick and decisive action is needed to halt the spread of TB. Multidrug-resistant TB is becoming a primary concern with public health officials. Specific plans and efforts, instigated by the Centers for Disease Control, have outlined the appropriate steps local public health workers, the medical community, and civic and community organizations should take in order to eliminate TB by the year 2010. With the creation of the Task Force on Drug Resistant Tuberculosis, Louisiana has a vehicle with which to combat its growing TB problem.


Tuberculosis in children in 1992.

Tuberculosis in children in 1992. In children, as in adults, tuberculosis is much commoner among minority population groups, in Louisiana particularly among blacks. Since 1986 tuberculosis in some states has increased notably; in Louisiana the increase is only now, in 1992, becoming apparent. Eighteen new cases in children under 20 were reported in 1991. Diagnosis in children still depends largely on history of contact and on the Mantoux tuberculin test. Treatment has changed markedly to a more intensive 6 month course including three or four drugs. Preventive treatment of tuberculin positive children is particularly emphasized because it will play an important role in achieving the stated public health goal of elimination of tuberculosis by the year 2010. With the increasing number of children exposed to tuberculosis, the increasing number of HIV-positive children at risk, and the rising number of multiresistant tubercle bacilli, vaccination with BCG must be considered.


New developments in mycobacteria identification: public health laboratory modernization. Clinical laboratory mycobacteriology has traditionally involved long delays for results, primarily due to the slow growth rate of most members of the genus Mycobacterium. Several new methodologies are now available that enable dramatic reductions in turn-around times. These methodologies include the Bactec TB System for isolation and drug susceptibility testing of Mycobacterium tuberculosis, the use of DNA probes, and high performance liquid chromatography (HPLC) for the identification of mycobacterial isolates. The spread of multidrug-resistant tuberculosis has made it imperative that laboratories take advantage of these new methodologies whenever possible. The Mycobacteriology Unit of the Louisiana Office of Public Health's Division of Laboratories has pioneered the use of these methodologies in a public health laboratory setting. Great reductions in turn-around times have been achieved and further reductions are expected as the methods are refined and adapted to the needs of a high-volume public health laboratory.


Supplemented low-protein diets protect the rat kidney without causing undernutrition. Low-protein diets supplemented with keto-analogues and essential amino acid (KA-EAA) mixtures or with EAA have been widely used to retard renal deterioration without affecting nutrition. These assumptions have recently been challenged in clinical studies and rest on little or no experimental data. The effects of EAA and KA-EAA supplementations have not been compared. We compared three groups of rats with subtotal nephrectomy that were fed (1) a 16% casein reference (R) diet, (2) a 6% casein plus EAA (A) diet, or (3) a 6% casein plus KA-EAA (K) diet with KA as amino acid salts. The three diets had the same energy and mineral contents, and they induced comparable growth. The two supplements had the same nitrogen content. The only difference found until month 3 was higher proteinuria and plasma urea levels in group R rats. Renal biopsies performed at month 3 showed more severe glomerular sclerosis and tubular changes in R rats than in A and K rats. From months 3 through 7, R rats developed higher plasma creatinine levels than did A and K rats (final median values: 167, 106, and 83 mumol/L; p < 0.04), had more proteinuria (232, 56, and 84 mg/day), and showed greater mortality rates. At the time the rats were killed, 2 R, 6 A, and 5 K rats had survived while receiving the diets. Examination of the remnant kidneys, regardless of time of death, showed that renal lesions were significantly worse in R than in A and K rats, with sclerosis affecting more than 50% of the glomeruli in 7 of 13 R, 4 of 14 A, and 4 of 15 K rats, and less than 25% glomeruli in 2 of 13 R, 10 of 14 A, and 10 of 15 K rats (A and K vs R: p < 0.03). In conclusion, restriction of nonessential amino acids compensated by EAA or by KA-EAA mixtures retards renal damage without affecting growth, but no real benefit of KA or EAA has been observed.


Effects of angiotensin-converting enzyme inhibition in diabetic rats with reduced renal function. To test the effect of converting enzyme inhibition (CEI) on diabetes, with or without renal insufficiency, we studied streptozotocin-induced diabetic rats, with or without reduced renal mass, which were treated with insulin in sufficient amounts to maintain glucose values in the mild to moderately hyperglycemic range. We found that diabetes increased glomerular filtration rate (GFR) (inulin clearance, 2.3 +/- 0.5 ml/min vs 1.9 +/- 0.1 ml/min; p < 0.05) and blood pressure (137 +/- 15 mm Hg vs 116 +/- 6 mm Hg; p < 0.05) but did not increase plasma atrial natriuretic peptide (ANP) values, when compared with control rats (72 +/- 38 vs 68 +/- 24 pg/ml). CEI decreased GFR and blood pressure to control values. In rats with diabetes and concomitantly reduced renal mass, hypertension, elevated ANP values, proteinuria, and glomerulosclerosis were prominent features. CEI was associated with reduced blood pressure (172 +/- 17 mm Hg vs 138 +/- 15 mm Hg; p < 0.05), without a concomitant decrease in GFR (1.1 +/- 0.1 ml/min vs 1.1 +/- 0.1 ml/min). Further, CEI reduced the elevated ANP values (140 +/- 34 pg/ml vs 66 +/- 19 pg/ml; p < 0.05) to those of control rats. CEI reduced proteinuria by 50% and ameliorated the histopathologic changes. In separate experiments, rats with 5/6th nephrectomy and hypertension but without diabetes were also found to have elevated ANP levels that decreased to control values with CEI. The data speak for a renal protective effect of angiotensin I-converting enzyme inhibition in this model but do not support a specific role for ANP in the model of diabetes with concomitantly reduced renal mass.


Calcium in human gallbladder bile.

Calcium in human gallbladder bile. Biliary calcium is believed to be of great importance in gallstone pathogenesis. These studies were therefore performed to determine if quantitative and/or qualitative differences in calcium are present in gallbladder bile from patients with and without gallstones. Bile was obtained by direct gallbladder aspiration from 68 obese patients undergoing elective gastric bypass surgery. Forty-five patients had no evidence of gallstones or sludge, 18 had cholesterol gallstones, and five had black pigment stones. Gallbladder bile was also obtained from 27 nonobese patients undergoing elective cholecystectomy (19 cholesterol; eight black pigment gallstones). For all patients, total calcium ranged from 1.50 to 16.44 mmol/L (mean: 6.05 +/- 0.31 mmol/L); free Ca++ ion ranged from 0.53 to 2.83 mmol/L (mean: 1.28 +/- 0.05 mmol/L). Considerable overlap was observed between obese and nonobese subjects and between patients with and without gallstones. For all patient groups, calcium, Ca++, and bound calcium increased linearly with increasing concentrations of bile salt. No significant differences in the slopes of these relationships were observed with obesity or gallstones. In contrast, free Ca++ ion was greater in gallbladder bile from gallstone patient groups throughout the entire range of bile salt. We hypothesize that this observed increase in Ca++ resulted from increased Gibbs-Donnan forces and excess gallbladder mucin present within the gallbladder bile of patients with gallstones.


Acyclovir transport by the human placenta. Genital Herpes simplex infection is noted increasingly in women of childbearing age and in neonates. Concern about transmission of herpes to the newborn has led to cesarean delivery of many pregnant women with a history of genital herpes. Severe herpes hepatitis has also been noted in pregnancy. Acyclovir is the drug of choice for this infectious organism. Because there are no data on the mechanism(s) of transport of this drug by the human placenta, this study addressed this issue. We used normal term human placentas. For study of overall placental transport of acyclovir, we used the single, isolated perfused cotyledon technique. For assessment of initial acyclovir uptake, we used microvesicles prepared from the maternal-facing syncytiotrophoblast. Overall transfer of acyclovir at therapeutic concentrations from maternal to fetal compartment was at a rate of about 30% that of a freely diffusible marker, antipyrine. The overall transport was not saturable, was not inhibited by 50-fold adenine concentration, and did not proceed against a concentration gradient. There was no placental metabolism of the drug. Fetal-to-maternal transfer of acyclovir was at a similar rate. In maternal-facing microvesicles net uptake of acyclovir was not saturable, but was temperature dependent and was inhibited by high concentrations of adenine and ganciclovir, but not by nucleosides (adenosine, cytidine, cytosine). These data are most consistent with a carrier-dependent, nucleobase-type uptake of the drug, but passive overall net transfer of acyclovir, dependent on its solubility characteristics.


Mineralocorticoid excess, dietary sodium, and myocardial fibrosis. Unlike the non-renin-dependent hypertension associated with infrarenal aorta banding, an abnormal accumulation of fibrillar collagen occurs within the adventitia of intramural coronary arteries and neighboring interstitial space of the left and right ventricles in arterial hypertension associated with primary or secondary hyperaldosteronism. Based on these findings it was suggested that this interstitial and perivascular fibrosis was mediated by mineralocorticoid excess (i.e., elevated plasma aldosterone relative to dietary sodium) and not ventricular loading. To further address the importance of mineralocorticoid excess, we examined the fibrous tissue response after 8 weeks in the following uninephrectomized rat groups receiving a high-sodium diet: D-aldosterone (ALDO) infusion (0.75 micrograms/hr sc, n = 16); deoxycorticosterone acetate (DOCA) administration (100 mg/kg/wk sc, n = 8); and administration of a mineralocorticoid-like substance, glycyrrhizic acid (GA; 1 gm kg/wk sc, n = 8). Compared with ALDO infusion and sodium deprivation (n = 9), untreated controls (n = 14), and uninephrectomized rats with high dietary sodium and no mineralocorticoid administration (n = 15), we found (1) hypertension and left ventricular hypertrophy with all forms of mineralocorticoid excess; (2) a rise in collagen volume fraction with ALDO, and an increase in perivascular collagen with DOCA; and (3) no observance of myocardial fibrosis with GA or experimental controls, including ALDO infusion and sodium deprivation. Thus, in the presence of enhanced sodium intake, chronic administration of ALDO or DOCA are associated with collagen accumulation in the myocardium, whereas with the mineralocorticoid-like compound GA, myocardial fibrosis was not seen.(ABSTRACT TRUNCATED AT 250 WORDS)


Endogenous urinary 3-hydroxyproline has 96% specificity and 44% sensitivity for cancer screening. A method for determining the endogenous urinary excretion levels of both 3-hydroxyproline and 4-hydroxyproline that may be useful for cancer screening of the general population and at the workplace is evaluated in this report. The excretion levels of 3-hydroxyproline and 4-hydroxproline were estimated in 97 patients with cancer and in 99 patients with various nonmalignant diseases and were compared with those of 211 healthy persons. Measurable 3-hydroxyproline peaks (by amino acid autoanalyzer) were absent from 93 samples from 211 healthy persons (44%), 50 of 99 patients with nonmalignant disease (50%), and 10 of 96 patients with cancer (10%). The levels of both 3-hydroxyproline and 4-hydroxyproline in cancer patients were significantly higher than those in healthy persons (p < 0.001 and p < 0.01, respectively) and those in patients with nonmalignant diseases (p < 0.05 and p < 0.01, respectively). Cancer patients were classified into three groups according to grade of cancer growth and invasion. The sensitivity of 3-hydroxyproline was 44% and higher than that of 4-hydroxyproline for the detection of stage II cancers (no distant metastasis); the sensitivities of both hydroxyprolines for the detection of stage I (very early cancer) were low. The specificity of these assays for healthy persons and patients with nonmalignant disease was 96% and 92% for 3-hydroxyproline, and 97% and 79% for 4-hydroxyproline, respectively. Urinary 3-hydroxyproline level should be further investigated as a cancer screening method for healthy persons in the community or the workplace, but appears unlikely to detect many cancers in the earliest stages.


Reduced membrane fluidity and increased glycation of membrane proteins of platelets from diabetic subjects are not associated with increased platelet adherence to glycated collagen. Platelets could contribute to vascular disease in diabetes through enhanced adherence to collagen exposed in injured vessels. Increased platelet adherence to collagen in diabetes could result from an alteration in platelets and/or platelet hypersensitivity to collagen that has been glycated to a greater extent. In this study, the adherence of platelets from diabetic or control subjects to glycated or nonglycated collagen coated onto glass surfaces was examined. Membrane fluidity of platelets was also determined, since decreased membrane fluidity associated with increased glycation of membrane proteins of platelets from diabetic subjects was shown in a previous study, and decreases in membrane fluidity have been shown by others to increase platelet adhesion. Thirteen diabetic subjects were compared with 13 age-and sex-matched control subjects. Collagen was glycated (9.7 nmol glucose/mg protein) by preincubation for 12 days in glucose-rich medium (500 mmol/L). A control solution of collagen incubated without glucose for the same time had 3.3 nmol glucose/mg protein. There were no differences in the adherence of platelets from diabetic and control subjects to nonglycated and glycated collagen-coated glass. The mean steady-state fluorescence polarization value (0.187 +/- 0.002) in 1.6-diphenyl-1,3,5-hexatriene-labeled platelets from diabetic subjects was significantly greater than in platelets from control subjects (0.174 +/- 0.002, p < 0.002); thus membrane fluidity in platelets from the group of diabetic subjects was decreased. The extent of glycation of membrane proteins from diabetic subjects (25.4 +/- 0.5 nmol glucose/mg protein) was significantly greater than from control subjects (20.2 +/- 0.4 nmol glucose/mg protein, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Mechanisms of glucagon-induced renal vasodilation: role of prostaglandins and endothelium-derived relaxing factor. The mechanisms underlying the renal hemodynamic responses (vasodilation and hyperfiltration) to an amino acid or protein load are currently unknown and are relevant to understanding the effect of dietary protein on the progression of chronic renal failure. Glucagon (GLC) has been suggested to be important in these renal hemodynamic responses, although the mechanism is again unclear. Thus we investigated potential mediators of the renal hemodynamic response to GLC in the anesthetized rat, including prostanoids and endothelium-derived relaxing factor (EDRF). The effects of glucagon alone and after pretreatment were tested as follows: (1) after baseline renal hemodynamic measurements done with clearance techniques, rats were given GLC alone (n = 5; 200 ng/min IV continuous infusion); (2) glucagon was given after pretreatment with the EDRF synthesis inhibitor nitro-arginine-methyl-ester (NAME; n = 6; 125 micrograms/kg/min intrarenal artery by continuous infusion); (3) glucagon was given after pretreatment with indomethacin (INDO; n = 6; 5 mg/kg IV bolus). Repeat clearances demonstrated that GLC infusion increased glomerular filtration rate (GFR; basal vs GLC, 0.87 +/- 0.04 ml/min vs 1.14 +/- 0.09 ml/min, p < 0.05); renal plasma flow (RPF; 4.10 +/- 0.18 ml/min vs 5.56 +/- 0.32 ml/min, p < 0.05) and decreased renal vascular resistance (RVR; 15.82 +/- 1.17 mm Hg/[ml/min] vs 10.72 +/- 0.65 mm Hg/[ml/min], p < 0.05). Intrarenal N-nitro-L-arginine-methyl-ester (NAME) infusion significantly reduced basal GFR (-20% +/- 8%, p < 0.05) and RPF (-43% +/- 2%, p < 0.05), while increasing RVR (+108% +/- 9%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


The pituitary-gonadal axis in experimental nephrotic syndrome in male rats. Basal and luteinizing releasing hormone-stimulated gonadotropin secretion were studied in male rats made nephrotic with puromycin, and in pair-fed and normal control animals. In addition, plasma concentrations of testosterone, androstenedione, estradiol, and estrone were measured in the three groups of animals. Urinary testosterone concentrations were also measured in the three experimental groups. The data showed that basal luteinizing hormone concentration was significantly elevated in the nephrotic group compared with the pair-fed and normal control groups. Gonadotropin response to luteinizing releasing hormone stimulation was not significantly different in the three groups, suggesting an intact hypothalamic-pituitary axis in nephrotic syndrome. Urinary testosterone concentration in the nephrotic animals was significantly higher than in the pair-fed and normal control groups. Plasma testosterone, androstenedione, estradiol, and estrone concentrations were significantly lower in the nephrotic and pair-fed animals than in the normal control animals, indicating possibly impaired gonadal steroidogenesis in these two groups that may be related to the catabolic state of the animals. It thus appears that urinary loss of protein-bound (sex hormone binding globulin-bound) testosterone in the nephrotic syndrome leads to increased basal secretion of luteinizing hormone, presumably as a result of increased luteinizing releasing hormone secretion. This occurs to compensate for the abnormal urinary testosterone loss and is an attempt to restore plasma testosterone concentrations to normal. The higher basal plasma luteinizing hormone concentration in the nephrotic group supports this conclusion.(ABSTRACT TRUNCATED AT 250 WORDS)


Amiodarone-induced endothelial injury is associated with phospholipase C-mediated hydrolysis of membrane phospholipids. Phospholipids accumulate within the lysosomes of various cells from individuals taking amiodarone. Studies on cultured cells suggest that inhibition of lysosomal phospholipase A1 and phospholipase A2 by amiodarone may be responsible for this derangement in phospholipid metabolism. Inhibition of lysosomal phospholipases by amiodarone has been suggested as a mechanism of its toxicity, but this relationship has not been clearly established. To examine this question, membrane phospholipids of cultured bovine pulmonary artery endothelial cells (BPAEC) were labeled with 14C-stearic acid, 3H-arachidonic acid, 14C-choline, or 14C-ethanolamine. Radiolabeled BPAEC were then exposed to various concentrations of amiodarone, and endothelial phospholipase activity was measured by isolating and quantifying various phospholipase products. These findings were compared to a standard indicator of endothelial cytotoxicity using 51Cr release. Six-hour exposures to 5 to 20 micrograms/ml amiodarone produced no BPAEC toxicity and were accompanied by some evidence of decreased phospholipid hydrolysis. At concentrations above 20 micrograms/ml, amiodarone caused significant BPAEC toxicity as indicated by 51Cr release, and this was closely associated with the liberation of substantial amounts of 3H-arachidonic acid and 14C-stearic acid from phosphatidylcholine and phosphatidylethanolamine. In BPAEC labeled with 14C-choline and 14C-ethanolamine, cytotoxic doses of amiodarone caused accumulations of 14C-phosphocholine and phosphorylethanolamine, expected products of phospholipase C, but without increases in phospholipase A products. We conclude that exposure of BPAEC to toxic concentrations of amiodarone is associated with extensive hydrolysis of phosphatidylcholine and lysophosphatidylethanolamine via a phospholipase C-specific mechanism, and suggest that this may be a mechanism in the pathogenesis of amiodarone toxicity.


The effects of extracellular calcium on prairie dog gallbladder ion transport. Recent studies suggest that experimentally induced gallstone formation is associated with altered gallbladder absorptive function. Moreover, elevated biliary levels of calcium have been implicated in the pathogenesis of cholesterol gallstones. Nonetheless, the relationship between gallbladder ion transport and biliary calcium remains obscure. We tested the hypothesis that extracellular calcium modulates gallbladder ion transport. Prairie dog gallbladders were mounted in an Ussing chamber, and short-circuit current (Isc), transepithelial potential difference (Vms), and tissue resistance (Rt) were measured. Tissues were randomly exposed to physiologic salt solutions containing the following concentrations of calcium: 0.01, 1.3, 5, and 10 mmol/L. Exposure of gallbladder epithelium to increasing calcium concentrations resulted in concomitant increases in Isc and Vms (p < 0.001), without altering Rt. Regression analysis demonstrated a curvilinear correlation between calcium and Isc (Y = 167 + 22.5x - 1.4 x 26; p < 0.001). We conclude that extracellular calcium may be a modulator of gallbladder ion transport.


Laminin B1 is preferentially expressed in the cortex of rat kidney and is not affected by cyclosporine administration. Cyclosporine has proven beneficial as an immunosuppressive agent for organ rejection in kidney transplants as well as in heart and liver transplants. Cyclosporine administration, however, is associated with certain adverse effects, one of the most important being chronic nephrotoxicity characterized by focal cortical scarring. Recent experimental data show involvement of type I and possibly type IV collagens in this process. Because laminin represents another potential extracellular matrix target, we examined the effects of cyclosporine administration in rats on the expression of laminin at the messenger ribonucleic acid (mRNA) and protein levels. In untreated normal rats, laminin B1 mRNA is preferentially expressed in the renal cortices, as demonstrated by northern blots. Daily administration of cyclosporine leads to focal cortical interstitial fibrosis and tubular atrophy by 4 weeks with, as shown previously, elevated procollagen alpha-1 (type I) mRNA levels at 1 and 4 weeks. In contrast, the amounts of message for laminin B1 remain identical after 1 week and 4 weeks of cyclosporine administration, despite the development of fibrosis at 4 weeks. Similar results were obtained with antilaminin antibody. We conclude that laminin is abundant in renal cortical tissues as compared with its medullary contents and is not altered in the process of renal cortical fibrosis induced by cyclosporine.


Metabolic disturbances in hypertension: results from the population study 'men born in 1913'. A clustering of metabolic disturbances has been indicated in hypertension. The distribution of such factors was assessed among hypertensives and normotensives in a general population sample of 644 men aged 67 years. Fasting serum insulin, glucose and triglyceride levels were measured. In this study hypertension was defined as DBP > or = 95 mmHg or present use of antihypertensives. Impaired glucose tolerance (IGT) or diabetes mellitus, hyperinsulinaemia (> or = 20 mU l-1) and hypertriglyceridaemia (> or = 2.3 mmol l-1) were defined as metabolic disturbances. When all these disturbances were present simultaneously a complete 'metabolic syndrome' was considered to be present. Hypertension was found in 185 (29%) men, IGT in 15%, diabetes mellitus in 11%, hyperinsulinaemia in 18% and hypertriglyceridaemia in 19%. Among hypertensives, 11 (6%) men had a 'metabolic syndrome', compared to 12 (3%) men in the normotensive group (P = 0.039). At least one metabolic disturbance was present in 109 (59%) of the hypertensive men, and in 173 (38%) of the normotensive men (P < 0.001). The prevalence rates of metabolic disturbances did not differ significantly between lean (BMI < 26 kg m-2) and obese (BMI > or = 26 kg m-2) hypertensives. Only hypertriglyceridaemia was more frequent in obese than in lean hypertensives (20% vs. 37%, P = 0.015). The 'metabolic syndrome' was found in 6% of all hypertensives, which was twice as common as in the normotensive population. The 'metabolic syndrome' was uncommon in both lean and obese hypertensives (5% vs. 7%, NS). These findings indicate that hypertension and metabolic disturbances may have a common underlying cause, at least in some individuals.


Association between high levels of growth factors in plasma and progression of coronary atherosclerosis. Although intimal proliferation of smooth muscle cells (SMC) is recognized as one of the key mechanisms in the development of atherosclerosis, our knowledge of the role of circulating growth factors for SMC in this process is limited. In the present study the plasma levels of platelet-derived growth factor (PDGF), beta-thromboglobulin (beta-TG), platelet factor 4 (PF 4) and total growth factor activity were determined in a group of 30 young postinfarction patients who had participated in an angiographic study of mechanisms associated with progression of coronary atherosclerosis. Significant correlations were found between the total growth factor activity in plasma and progression (r = 0.42, P < 0.05), as well as severity (r = 0.52, P < 0.01), of global coronary atherosclerosis. Attempts to identify the nature of the total growth factor activity indicated that less than 20% could be attributed to PDGF, the major serum mitogen for SMC. PDGF levels determined by radioimmunoassay were not related to progression or severity of global coronary atherosclerosis, but showed a significant association with the number and severity of distinct stenoses (r = 0.40, P < 0.05). Due to the retrospective design of this study, it is not possible to conclude whether there is a causal relationship between circulating growth factors and development of coronary atherosclerosis.


Occurrence of species of low-density lipoprotein with defective clearance in patients with primary moderate hypercholesterolaemia. Recent studies have shown that one cause of primary moderate hypercholesterolaemia is familial defective apolipoprotein B-100 (FDB), a condition in which a mutation in apolipoprotein B-100 (apo B-100) causes low-density lipoproteins (LDL) to bind poorly to LDL receptors. One specific mutation, a glutamine-for-arginine transformation at position 3500 of apo B-100, has been reported to produce FDB. However, other mutations in apo B-100 might also cause FDB. The present study was designed to determine whether some patients with hypercholesterolaemia, who do not have the 3500 defect, may have a slowly cleared subfraction of LDL compatible with other forms of FDB. It was postulated that slowly removed LDL should accumulate excess cholesterol ester and hence be less dense than normal LDL. If so, in patients who are heterozygous for FDB, two forms of LDL might be separable by ultracentrifugation. To test this hypothesis, less-dense (d = 1.030 g ml-1) and more-dense (d = 1.040 g ml-1) subfractions of LDL were isolated from a patient with proven FDB (3500 mutation); the two forms of LDL were labelled with different isotopes of radioiodine and re-injected into the patient. The less-dense form was removed much more slowly (0.285 pools day-1) than more-dense LDL (0.570 pools day-1). This finding appeared to confirm the validity of the approach. The same procedure was then applied to 18 other patients having elevated LDL cholesterol but not the 3500 mutation. In 13 patients, the two forms of LDL were removed at essentially identical rates, suggesting that they did not have an abnormal form of LDL. In the other five, less-dense LDL were removed at a significantly slower rate than more-dense LDL; this finding suggests that a significant portion of patients with moderate hypercholesterolaemia have an abnormal LDL species, which is not the 3500 mutation, but delays clearance of LDL from the circulation.


The relationship between the transfer factor obtained at rest, and arterial oxygen tension during exercise, in patients with miscellaneous pulmonary diseases. Forty-one consecutive patients with the symptom 'exertional dyspnoea' were referred to the Department of Clinical Physiology for evaluation. Pulmonary fibrosis and chronic obstructive pulmonary disease were the most common diagnoses but other diagnoses were also represented. Some patients had no clinical diagnosis or radiological signs. All patients underwent exercise testing with sampling of arterial blood for blood gas analysis and pulmonary function testing including measurement of the transfer factor (carbon monoxide diffusing capacity) at rest. Independent of spirometric findings and diagnosis a significant correlation (r = 0.80, P < 0.001) was shown to exist between the transfer factor measured at rest and the arterial oxygen tension at maximal exercise level. We recommend measurement of the transfer factor as a screening test for exertional hypoxaemia and suggest that exercise blood gas analysis only seems necessary in patients with a transfer factor between 55% and 80% of the predicted value.


Increasing parathyroid hormone concentrations in untreated primary hyperparathyroidism. Twenty-four patients with mild to moderate primary hyperparathyroidism were followed for an average of 2.45 years with serial determinations of serum ionized calcium and intact parathyroid hormone (PTH). For the entire group serum ionized calcium remained stable, whereas serum PTH increased significantly. Eleven patients (group 1) demonstrated a significant increase in PTH with time. The remaining 13 patients formed group 2. Comparison of the changes (%) in each subgroup showed a small but significant increase in serum ionized calcium of 2.6% with time in group 1, while serum PTH increased by 78%. In group 2 serum ionized calcium remained stable whereas PTH increased modestly by 22%. Serum concentrations of creatinine were stable throughout the follow-up period in both groups. Despite the greater precision of serum ionized calcium, measurements of intact PTH are evidently more sensitive than measurements of serum ionized calcium for the detection of progression in primary hyperparathyroidism.


Diagnosis of acute symptomatic aortic aneurysm--ultrasonography an important tool. Symptomatic aortic aneurysm is an extremely acute condition with manifest or threatening aortic rupture. The mortality is high and urgent surgery is essential and often life-saving. A correct diagnosis needs to be made without delay, a fact which places great demands on the doctor--often not a surgeon--who is first consulted by the patient. The differential diagnosis and emergency management are discussed here against the background of the course of events in four patients with aortic aneurysm who were referred erroneously for admission to a coronary intensive care unit during a 12-month period. Two of the patients died. The ultrasonographic findings were decisive for the outcome in the two surviving patients and yielded a rapid diagnosis in one further case. Ultrasonography is recommended as the method of first choice for verifying or excluding this condition when it is suspected on clinical grounds.


Survival in 91 adults with acute myelogenous leukaemia treated with 1-6 intensive courses of chemotherapy. Ninety-one patients with acute myelogenous leukaemia (AML) aged 17-59 years were treated with a chemotherapy programme which could be completed within 30 weeks for patients who achieved complete remission (CR). Four courses included daunorubicin, cytarabine and thioguanine, while two courses included amsacrine, etoposide and cytarabine. Sixty-five patients obtained CR (71%), more often in patients below (82%) than above (60%) 40 years of age (P = 0.03). Five patients underwent allogenic bone-marrow transplantation, and one patient received an autologous bone-marrow transplant after relapse. Five patients developed central nervous system leukaemia. The overall actuarial 3- and 5-year survival was 29% and 21%, respectively; for patients who obtained CR the corresponding survival rates were 40% and 30%, respectively. Patients below 40 years of age appeared to fare better (5-year survival 26%) than older patients (5-year survival 16%). The estimated disease-free survival rate was 26% at 3 years and 22% at 5 years. The main advantage of this regimen is that results compare favourably with those obtained with other regimens were achieved, without exposing patients to long periods of maintenance therapy.


Immunoreactive interleukin-6 in serum of patients with B-lymphoproliferative diseases. Serum immunoreactive interleukin-6 (ir-IL-6) concentration was measured by radioimmunoassay in nine patients with chronic lymphocytic leukaemia (CLL), 16 patients with multiple myeloma (MM), 12 patients with monoclonal gammapathy of undetermined significance (MGUS), 22 patients with primary Sjögren's syndrome (SS), and in 32 control subjects. Measurable quantities of ir-IL-6 were detected in every sample studied. Patients with MGUS and SS had significantly higher serum ir-IL-6 (mean +/- SD) concentrations (337 +/- 92 ng l-1 and 299 +/- 100 ng l-1, respectively) than controls (92 +/- 77 ng l-1) and patients with CLL and MM (120 +/- 32 ng l-1 and 113 +/- 58 ng l-1, respectively). Longitudinal studies of ir-IL-6 concentration in a few patients with MM showed a decrease before remission and an increase prior to relapse, but no consistent pattern was detected. In conclusion, we found that serum ir-IL-6 levels are higher in patients with benign hypergammaglobulinaemic states than in patients with malignant neoplastic B-cell disorders.


Haematologic effects of granulocyte-macrophage colony stimulating factor in a patient with thiamazole-induced agranulocytosis. A 61-year-old female patient, treated for hyperthyroidism with thiamazole, developed a severe maturation arrest in the granulocytic lineage and a total agranulocytosis. Subcutaneous GM-CSF was started immediately and given for 6 days. Bone marrow samples were taken before GM-CSF therapy and on days 3 and 8. An increased number of colonies per 10(5) bone marrow cells documented before institution of GM-CSF treatment was followed by a gradual decline to normal values. An increase of granulocyte count to > 0.5 x 10(9) l-1 was recorded on the 4th day of treatment and was preceded by an increase in the number of immature granulocyte precursors in the bone marrow on day 3. The patient was discharged on day 8 and experienced no adverse effects of GM-CSF treatment. Haematopoietic growth factor therapy has a place in the management of patients with drug induced neutropenia/agranulocytosis, which should be further delineated by prospective studies.


The bone mineral density in acquired growth hormone deficiency correlates with circulating levels of insulin-like growth factor I. Insulin-like growth factor I (IGF-I) is an important anabolic factor for osteoblasts in vitro. Low plasma levels of IGF-I have been observed in young men with osteoporosis. In the present study, we have studied bone mineral density (BMD) and the circulating levels of IGF-I and growth hormone (GH) in adults with acquired GH deficiency. BMD was determined by dual-energy x-ray absorptiometry in 17 men and 12 women (age 27-54 years). Spinal BMD was positively correlated with the plasma levels of IGF-I (r = 0.43, P = 0.019), with the median of GH values obtained by repeated sampling at night (r = 0.43, P = 0.0019), and with the peak of GH values during GHRH provocation test (r = 0.49, P = 0.039). The total BMD was positively related to plasma IGF-I and median of GH values, but not to peak GH by GHRH provocation. In a multiple regression analysis model, IGF-I, peak GH by GHRH provocation test and duration of GH deficiency explained 49% of the variation in spinal BMD. As compared to healthy controls, total, but not spinal, bone mass was lower in men with GH deficiency, but no clinical symptoms of osteoporosis were observed. The positive relationships between BMD and circulating IGF-I and other indices of GH secretion suggest that IGF-I has an endocrine effect on bone mass.


Testosterone/epitestosterone ratio in urine: a possible diagnostic tool in the disclosure of exogenous testosterone administration. A 37-year-old woman presented with a history of secondary amenorrhoea and hirsutism for 4 years. She had elevated serum levels of testosterone and dihydrotestosterone, and decreased serum levels of sex hormone binding globulin and oestradiol. Almost daily use of a testosterone-containing ointment in the vulvar region for 6 years was disclosed as the cause of the hyperandrogenism. Serum testosterone, testosterone excretion rate in urine and testosterone/epitestosterone ratio in urine were determined at fixed intervals 24 h before and 48 h after application of the testosterone-containing ointment. There was a rapid increase in serum testosterone, with a peak level after 4-6 h. The testosterone excretion rate and the testosterone/epitestosterone ratio in urine peaked after 2-4 h. After 48 h the serum testosterone level was still about twice the basal value. The testosterone/epitestosterone level was over the 'doping limit' of 6 for 28 h. We conclude that determination of the testosterone/epitestosterone ratio in urine would have disclosed exogenous testosterone administration in this patient. We recommend this test for patients in whom exogenous testosterone administration is suspected.


Two UV-induced episodes of myelitis in a patient with systemic lupus erythematosus. Two flares of acute myelitis were observed in a 31-year-old woman with previously known mild SLE. The two myelitic episodes both occurred within 1 week after intense sun exposure, and for this reason photobiological induction of the manifestation is considered likely. The diagnostic utility of MRI in the acute situation and the possible influence of sex-steroids on SLE manifestations are also illustrated by this case.


On estimating processing variance: commentary and reanalysis of Kail's "Developmental functions for speeds of cognitive processes". A recent paper by Kail (1988) in this journal appears to contain a significant error in the data analysis. The "goodness-of-fit" coefficients reported which suggest that overall about 94% of the variance can be accounted for by the model seem to be a substantial overestimation as a result of inappropriate procedures for statistical modeling. Using the data made available to us by Kail, we have reanalyzed these results. The corrected values range from 0.9 to 92.1% for the individual tasks with an overall average between 40 and 60%. We suggest that the support for the original conclusions is considerably weaker than reported.


Evidence for global developmental change is intact. In this article, I argue that most of the claims made by Morrison, Morrison, and Keating (1992) do not undermine the key results of the Kail (1988) study and that, contrary to their claims, the evidence still provides support for the original conclusion that a global mechanism is implicated in age-related change in speed of processing.


Covert orienting to central visual cues and sport practice relations in the development of visual attention. This study examines the development of controlled covert orienting of visual attention, according to the age and the level of performance of tennis players. Practicers and nonpracticers age 13, 16, and 25 participated in a covert orienting task. On each trial, subjects responded to a target which appeared in one of four locations arrayed horizontally across the display. Three central cues were used: neutral, the cue did not specify in which location the target would appear; valid, the target was present in the cued location on 80% of the trials; invalid, the target was present in one of the uncued locations on the remaining 20% of the trials. The results showed that (1) practicers were not faster than nonpracticers in processing the signals, (2) observers of all ages oriented attention voluntarily to the cued locations, (3) central cues had a smaller effect on older and practiced subjects, and (4) developmental and sport practice factors had similar effects on orienting efficiency. The implications of these findings for theories of attentional development are discussed.


Operativity and the superordinate categorization of artifacts. Relations between typical and atypical exemplars of superordinate categories are low in figurative similarity, i.e., similarity based in appearance or in spatial/temporal context. Operativity, as an emergent competence to overcome figurative cues and establish nonfigurative relations, might be expected to contribute to superordinate categorization. The present study assessed the relative consistency of age-equivalent preoperational and concrete-operational groups of first graders across two categorization tasks employing color drawings of exemplars of superordinate artifact categories. Concrete-operational subjects categorized two exemplars together on a Sample-Match Task if they had previously included both exemplars under the same category on a Category-Membership Task. In addition to membership in the same category, preoperational subjects required that both exemplars be typical before categorizing them together on the Sample-Match Task. The cognitive levels did not differ in their category membership decisions. Results are discussed in terms of both utilization and acquisition of superordinate knowledge.


The role of attention in children's time perception. This study tested the role of attention in 7- to 9-year-old children's time estimation. Based on an attentional model of time estimation, it was hypothesized that prospective estimates of short intervals are a function of the degree to which a child is occupied with the passage of time and is focusing his or her attention on estimating the exposure time of a stimulus. Two experiments with two different manipulations on attentional focus were conducted. Eighty children were exposed to two types of light bulbs, one a big bulb kindled with high intensity and the other a small one kindled with low intensity. The light bulbs were kindled for different intervals ranging from 3 to 10 s. In both experiments children estimated the lighting time of the bulbs in each condition by a reproduction method. In the first experiment prospective time estimates were found to be significantly longer than retrospective ones. In the second experiment children gave shorter time estimates when their attention was attracted away from the time estimation task than when it was not. In both experiments the attentional hypothesis was supported. In addition, support for the "more is more" hypothesis was obtained. Implications for understanding children's time perception processes are discussed.


Counting knowledge and skill in cognitive addition: a comparison of normal and mathematically disabled children. The relationship between counting knowledge and computational skills (i.e., skill at counting to solve addition problems) was assessed for groups of first-grade normal and mathematically disabled (MD) children. Twenty-four normal and 13 MD children were administered a series of counting tasks and solved 40 computer-administered addition problems. For the addition task, problem-solving strategies were recorded on a trial-by-trial basis. Performance on the counting tasks suggested that the MD children were developmentally delayed in the understanding of essential and unessential features of counting and were relatively unskilled in the detection of certain forms of counting error. On the addition task, the MD children committed many more computational errors and tended to use developmentally immature counting procedures. The immature counting knowledge of the MD children, combined with their relatively poor skills at detecting counting errors, appeared to underlie their poor computational skills on the addition task. Suggestions for future research are presented.


Clarifying the role of shape in children's taxonomic assumption. When asked to find a new referent of a novel label children tend to ignore thematic relations (e.g., the relation between a spider and its web) and focus instead on taxonomic relations (e.g., the relation between a spider and a snake). The precise nature of children's taxonomic assumption has not been clear, however. One possibility is that the taxonomic assumption reduces to a "similar-shape rule": perhaps children tend to select objects of the same taxonomic kind when asked to extend new labels simply because these objects are more similar in shape than objects which are only thematically related. Sixty children between 3 and 5 years of age participated in three studies which examined children's attention to thematic relations, similarity of shape, and taxonomic relations when extending novel object labels. The findings indicated that shape has some primacy in children's expectations about object label reference, yet when shape is not available as a guide, children also take taxonomic kind into consideration when searching for new referents of novel labels. Thus children make use of a relatively rich and somewhat varied set of expectations to guide their inferences about object label reference.


Clarithromycin vs penicillin in the treatment of streptococcal pharyngitis. Streptococcal pharyngitis, caused by group A beta-hemolytic streptococci (GABHS), is among the most common infections seen by primary care physicians. Because the illness can result in rheumatic fever, early eradication of infection is important. Penicillin has been the standard treatment for GABHS pharyngitis for over four decades, but reports of bacteriologic failure with this drug in recent years have led to trials of alternative antimicrobials. In this investigator-blind, randomized multicenter trial (30 centers), oral clarithromycin, 250 mg twice daily, or oral penicillin VK, 250 mg three times daily, was given to outpatients > or = 12 years old with GABHS pharyngitis as documented by positive cultures for Streptococcus pyogenes and positive rapid immunoassay tests. The clinical and bacteriologic efficacy of clarithromycin was compared with that of penicillin in the 356 evaluable patients. Safety analysis was performed in all patients who had received at least one dose of the study drug (N = 453). Overall, clinical outcomes were comparable in the two groups. However, more clarithromycin-treated patients than penicillin-treated patients had resolution of sore throat (94% vs 86%, P = .014) and disappearance of pharyngeal erythema and exudate (89% vs 82%, P = .05). Bacteriologic cure rates were higher in clarithromycin-treated patients (95% vs 87%, P = .009). No serious adverse events were observed in either group. This study suggests that clarithromycin twice daily is as effective and as well tolerated as penicillin in the treatment of streptococcal pharyngitis.


Patients' attitudes regarding chaperones during physical examinations. This study was undertaken to determine the preference of patients concerning the presence of a chaperone during physical examination of the breasts, genitals, rectum, heart and lungs, or abdomen. The study was designed to quantify preference differences between male and female patients and between teenagers and adults, and to determine whether the sex of the examining physician influenced chaperone preference. Preference survey data were obtained from 251 female subjects and 201 male subjects over the age of 13 years who visited a family practice center in a midwestern urban community. The majority of patients of either sex and all ages did not care if a chaperone was present. However, substantial proportions of adult women (29%) and female teenagers (46%) preferred that a chaperone be present during a breast, pelvic, or rectal examination by a male physician. Thirty-six percent of adult women and 63% of female teenagers wanted a chaperone present during a first examination of these regions. Adults of both sexes felt the nurse would be the best chaperone, whereas teenagers ranked a parent first and the nurse second. Patients indicated that they felt comfortable asking for a chaperone. Although most patients have no strong preference, female patients, especially female teenagers, should be given the option of having a chaperone present during an examination of the breasts, pelvis, or rectum by a male physician.


Relationship between Pap smear performance and physician ordering a mammogram. Although Pap smear screening for cervical cancer in general has been successfully implemented, mammography screening for breast cancer remains relatively underused. Patients having one screening test are more likely to have other screening tests performed. The objective of this study was to determine whether visits by women for Pap smears serve as opportunities for physicians to order a screening mammogram. A matched case-control design was used for this retrospective study. Eligible women included those over 50 years of age who had no history of breast cancer or mastectomy and who had made at least one visit to a family practice residency program during the 2-year study period. Cases were randomly selected from women who had mammograms performed. For each case, one control subject who did not have a mammogram was matched by age and number of visits. A chart audit was performed to collect data on the characteristics of these women and whether they completed their screening tests. The adjusted odds ratio (controlling for the patient's age and number of physician visits) for mammogram completion among women who had a Pap smear compared with those who did not was 6.67. This effect persisted after controlling for other confounding factors using logistic regression. Performing a Pap smear appears to serve as a prompt for the physician to order a screening mammogram. That physicians appear to provide screening tests, particularly Pap smears and mammograms, as a package of services should be considered when future efforts to improve implementation are made.


Outpatients' attitudes regarding advance directives. Although many bedside ethical dilemmas can be avoided if patients discuss their wishes regarding the use of life-prolonging treatment and aggressiveness of care, many physicians are reluctant to raise this issue with their patients. Physicians may wait for such discussions until a patient is ill or elderly or until the patient raises the issue first. Three hundred adult patients visiting their family physician's office were asked to complete a 19-item questionnaire. In addition to providing demographic information, they were asked whether they had discussed their wishes regarding life-prolonging treatments with their physician; what their attitude was toward having these discussions in various situations; whom they wanted to initiate the discussion, and with whom else they had discussed their wishes. Of the respondents who had not previously discussed their wishes with their physician, 68% wanted the physician to initiate the discussion. Only 11% did not want their physician to bring up the subject. A majority of respondents in all age groups thought it was somewhat or very important to discuss this matter both when healthy and when very ill. Very few patients would be upset if their physician raised the issue of life-prolonging treatment even if he or she did so during an initial patient visit. To avoid problems later, physicians should take an active role by raising these questions early in the patient-physician relationship rather than waiting for the patient to do so.


The impact of a patient survey or a physician reminder on the provision of adolescent preventive health care. The objective of this study was to determine if the use of a patient survey or a chart stamp could increase the implementation of adolescent preventive health care in a family practice center. Subjects were all patients 13 to 18 years old (date of birth 1972 to 1977), who visited the Aultman Family Practice Centers from October 1, 1989, through September 30, 1990 (N = 801 patient visits). Three different 1-month interventions (patient questionnaire, physician stamp, and both patient questionnaire and physician stamp) as well as a 1-month control period were implemented. The effect of the intervention on adolescent preventive health care was measured by review of documentation in the patient's chart. Those charts that indicated that either the questionnaire or stamp had been used showed significantly more documented discussion of issues relating to mood, injury, sexuality, exposure to toxins, and lifestyle (all P < .01). These discussions most commonly took place during a visit for a physical examination. The percentage of visits with documented discussions did not vary significantly according to type of reminder, nor with any physician or patient characteristic. The use of a reminder, especially in the context of an office visit for a physical examination, significantly increased the implementation of adolescent preventive health care in this family practice center.


Coding and reimbursement of primary care debridement and excision procedures. Current medical practice requires physicians to accurately report services provided to patients. Patient billing for debridement and excision procedures involves the selection of specific 1992 Physicians' Current Procedural Terminology codes. Although a site-specific surgical procedure code often yields higher reimbursement than a general procedure code, physicians should select the code that most accurately reflects the procedure performed. This review identifies the codes used to report destruction and excision procedures performed by primary care physicians. Included in this review are skin debridement, burn debridement, excision of benign and malignant lesions of the skin and subcutaneous tissue, cyst and ganglion excision, nail excision, anorectal lesion excision, shave, paring, and skin tag excision procedures, and foreign body removal. The Health Care Financing Administration's relative value units and one state's published Medicaid payment rates are included for each procedure code. Instructions are provided for selecting between multiple coding options when more than one code describes the service provided.


Gastroesophageal reflux disease in adults: pathophysiology, diagnosis, and management. Gastroesophageal reflux disease (GERD) refers to symptoms or tissue damage that result from gastroesophageal reflux. Reflux esophagitis is a subset of GERD and implies the presence of esophageal inflammation, ie, esophageal erosions that are visible endoscopically, or nonerosive inflammation that can be documented by biopsies. Heartburn is the most common and specific symptom of GERD. In some patients, chest pain or respiratory symptoms may be the only presenting signs. In patients aged < 50 years with uncomplicated GERD, empiric therapy (typically with antacids or an H2-receptor antagonist) is appropriate. For older patients, those with complications, and those whose symptoms do not respond to empiric therapy, endoscopic evaluation is indicated. Many patients will improve with standard twice-daily dosing of an H2-receptor antagonist. However, GERD is generally more resistant to antisecretory pharmacologic therapy than is peptic ulcer disease. Those patients who fail to respond to standard dosing of an H2-receptor antagonist may get relief from high-dose H2-receptor antagonists or omeprazole therapy.


Laboratory outbreak of Q fever.

Laboratory outbreak of Q fever. An outbreak of Q fever in a university department where sheep placentas were being used for research is described. Of six persons exposed to the sheep, four had positive titers with only one person developing an acute febrile illness and liver disease. This report illustrates the value of the family physician obtaining an occupational history and conducting an outbreak investigation.


Steroidogenesis in Fundulus heteroclitus. IV. Dichotomous effects of a phorbol ester on ovarian steroid production and oocyte maturation. The possible role of protein kinase C (PKC) activation in mediating the stimulatory actions of a Fundulus pituitary extract (FPE) on ovarian steroidogenesis and oocyte maturation was investigated. The phorbol ester, phorbol 12-myristate 13-acetate (PMA), alone slightly increased basal 17 alpha-hydroxy,20 beta-dihydroprogesterone (DHP) and 17 beta-estradiol (E2) synthesis and significantly stimulated germinal vesicle breakdown (GVBD). Addition of FPE promoted synthesis of DHP, testosterone (T), and E2, and initiated GVBD. Phorbol ester inhibited FPE-induced steroidogenesis but increased the number of oocytes that underwent GVBD. Phorbol ester also markedly impeded induction of steroidogenesis by dibutyryl cAMP and differentially affected the conversion of 25-hydroxycholesterol, pregnenolone, or progesterone to DHP, T, and E2: DHP production was not affected; T production diminished; and E2 synthesis increased (T aromatization also increased). These results suggest an inhibitory role for the PKC pathway on FPE-induced ovarian steroid production, with PMA appearing to affect various steroidogenic steps. The stimulatory action of PMA on oocyte maturation seems to be independent of follicular steroid production since aminoglutethimide, an inhibitor of steroidogenesis, did not block PMA-induced GVBD. Moreover, PMA had a marked stimulatory effect on GVBD in denuded oocytes. Thus, in contrast to the inhibitory role found for the PKC pathway on ovarian follicular steroidogenesis, activation of PKC in the oocyte may serve as a signal-transducing mechanism leading to GVBD.


Continuous cell movements rearrange anatomical structures in intact sponges. Time-lapse cinemicrography was used to record the active movements of cells in living intact sponges. Each of the three main cell types (pinacocytes, mesohyl cells, and choanocytes) continuously moved and rearranged themselves so that the internal anatomy of the sponge was continuously remodeled. The shape and appearance of the sponges anatomical structures often changed substantially within a few hours. The most motile were the mesohyl cells, with many moving as fast as one cell-length per minute (15 microns/min). Mesohyl cell locomotion was often accompanied by displacements of spicules, canals, and choanocyte chambers; the patterns of these displacements suggested that the mesohyl cells were providing the motive forces for these rearrangements. The locomotion of the pinacocytes varied according to position: those along the outer sponge margins were most active, whereas those in other parts of the surface moved relatively little. Choanocytes were never observed to undergo independent locomotion but were always found grouped together in choanocyte chambers. These choanocyte chambers interacted with pinacocytes and mesohyl cells to form excurrent canals, which continuously moved, fused with, and branched from one another. These observations suggest that the experimental phenomenon of sponge cell-reaggregation and reconstitution, discovered by H. V. Wilson, represents an extreme version of morphogenetic processes that normally go on continuously within intact sponges. The results from the present study also suggest that these cellular rearrangements are controlled by active cell movements and behavioral responses that include but are not limited to selective cell adhesion.


Effects of diapause on lethal yellow (Ay/Ay) mouse embryos. One of the problems in studying early acting recessive lethal genes is recognizing the homozygotes prior to their demise. Molecular probes can assist in this task, but their use generally requires removal of cells and consequent damage to the embryo, which may compromise its subsequent development. The present study was undertaken in an attempt to distinguish intact, living, lethal yellow (Ay/Ay) embryos from Ay/ae and ae/ae littermates before implantation by placing them in implantation delay or diapause. After 2 days in the reproductive tract of prepubertal females, the great majority of presumptive lethal Ay/Ay embryos has failed to hatch from the zona pellucida and they exhibited a marked deficiency of cells relative to controls, particularly in the inner cell mass. This argues against a stage-specific role for the gene in implantation.


Sexually differentiated mechanisms of sterility in interspecific hybrids between Oryzias latipes and O. curvinotus. Fertility of interspecific hybrids between Oryzias latipes and O. curvinotus was examined. F1 females were able to lay eggs but males were sterile. Histological examination of the ovaries of hybrids revealed that oogenesis does not proceed normally in spite of the apparent fertility. Most oocytes degenerated at the pachytene stage of the meiotic prophase, and only a few entered the diplotene stage to develop into ova. Hybrid males could induce females to spawn eggs, an indication that they had differentiated completely into true males. However, they did not produce fertile sperm. Most germ cells in testes of hybrids passes through almost the entire process of spermatogenesis, but deviations from the normal course of events were observed during spermiogenesis. The condensation of chromatin in spermatids occurred, but the diameters of sperm heads were about 1.5-fold larger than those of normal ones. Prominent abnormalities were apparent in the quantity and arrangement of microtubules in the cytoplasm. Abnormal spermatozoa were phagocytized by Sertoli cells. These observations indicate that the mechanisms of impaired gametogenesis in these interspecific hybrids are sexually differentiated.


Contribution of rodents to postmortem artifacts of bone and soft tissue. Postmortem disturbance of human remains by rodents extends beyond production of characteristic tooth mark artifacts in dry bones. Three case examples are presented that demonstrate a spectrum of rodent damage to dry and fresh bone and to fresh and mummified soft tissue. In one case, human remains are used for nesting purposes. Rodents are also noted to be vectors of bone transport. Rodent activities can affect bone recovery, human identification, and interpretation of artifacts to bone and soft tissue. Guidelines to differentiate soft tissue artifacts caused by rodents and carnivores are suggested.


Ultraviolet radiation and its role in wound pattern documentation. The history of ultraviolet illumination in photography is discussed. Particular attention is devoted to the forensic aspects of ultraviolet photography as it relates to patterned injury on human skin. The authors discuss the theory underlying ultraviolet illumination of wounds on skin as well as the equipment required for this type of imaging.


The detection and documentation of trace wound patterns by use of an alternative light source. This article is a discussion of the use of narrow-band light sources coupled with cameras equipped with band-pass filters to document patterned injuries on human skin. Several case reports are included.


A statistical analysis of successional patterns in carrion-arthropod assemblages: implications for forensic entomology and determination of the postmortem interval. A set of statistical protocols is proposed for analyzing carrion-arthropod succession in forensic entomology investigations. A total of 23 carrion-arthropod data sets from temperate, tropical, desert, and coastal environments were assembled in a standard format and analyzed using randomization tests and methods derived from quantitative community ecology. The data were analyzed in three ways. First, patterns of arthropod visitation on nonhuman carcasses were analyzed in each of the 23 cases. Analysis revealed two groups of taxa: those that persist on the carcass over a single time interval (= nonreoccurring taxa, 80% of the taxa) and those that appear, leave, and reappear over time on the carcass (= reoccurring taxa, 20%). Reoccurring taxa, which can confound estimation of the postmortem interval (PMI), were found in 6 classes, 12 orders, and 29 taxonomic families of arthropods, including some forensically important taxa (for example, calliphorids, sarcophagids, histerids). The recognition that reoccurring taxa exist and that they are found in forensically important groups is an early step toward factoring in their potential importance in future entomological investigations. Second, temporal changes in the taxonomic composition of the carrion-arthropod community were studied by quantifying the degree of taxonomic similarity between pairwise combinations of time-specific samples of the succession. In 13 of the 18 illustrated cases, the midsuccessional samples, owing to their higher species richness, were taxonomically more similar to all other pairwise samples, on the average, than early and late successional samples which were poorer in species. Variability in taxonomic composition is the norm for most periods of the succession; however, in 17 of the 23 cases, some successional periods (particularly endpoint samples) revealed no changes in arthropod species composition (= matching sample-pairs). When applied to medicolegal cases, it is suggested that data sets with large fractions of matching sample-pairs should produce wider-ranging PMI estimates, on the average, than data sets with smaller fractions of matching sample-pairs. Third, Monte Carlo simulation was applied to each of the 23 assemblages to test specific hypotheses about community-wide patterns of arthropod visitation times on nonhuman carcasses. Simulation results revealed that arthropod residence times in the majority of cases (13 or 56%) followed a "clumped" succession model, whereas, the remaining 10 cases (44%) showed a more "uniform" spacing pattern of residence times on carcasses. Comparison of species accumulation curves for observed and simulated data further revealed that among the 13 "clumped" cases, most (9 or 69%) followed a "clumped, early" model (rather than "clumped, midterm" or "clumped, late" models).(ABSTRACT TRUNCATED AT 400 WORDS)


Transferrin (TF) typing from semen stains using isoelectric focusing and immunoblotting: correlation of TF types among blood, semen, urine, and vaginal secretion. We describe a method for obtaining nondistorted and reproducible transferrin (TF) typing from liquid semen and semen stains. Isoelectric focusing of TF isoproteins on polyacrylamide gel (IEF-PAGE, pH 4 to 6.5) was accomplished using a 0.5 mm thick gel. The separated isoproteins were then visualized by immunoblotting with TF-specific antibody. Pretreatment of semen samples with neuraminidase enhanced the TF band resolution. The method was reliable, sensitive and simple, with a high resolution. When maintained at room temperature, laboratory-prepared semen stains were TF-typable for up to at least 50 weeks. The TF types in semen stains were correlated with the types found in the corresponding blood and urine samples. TF typing could therefore provide an additional discriminant characteristic in the forensic examination of semen stains. An evaluation of TF typing by IEF-PAGE and immunoblotting was also performed on casework samples submitted to our laboratory.


The decision theory of paternity disputes: optimization considerations applied to multilocus DNA fingerprinting. The solution of paternity disputes using results from scientific analyses is studied from a decision-theoretical viewpoint. Two alternative approaches to decision making, the so-called 'Bayes' and 'Minimax' strategies, are described and discussed. If prior probabilities of paternity are exactly known, then Bayes decisions are (a) independent of the source of evidence and (b) optimal with respect to average losses caused by wrong decisions. However, it is concluded that Minimax decisions, which depend upon the employed test system but not upon prior probabilities, are more appropriate in paternity cases if equal prior good will towards disclaimed children and alleged fathers is demanded. It is further demonstrated that, when major evidence about paternity comes from multilocus DNA fingerprinting, prior probabilities must be known quite accurately for Bayes decisions to be superior with respect to average losses. Finally, we are able to show that 'quasi' Bayes decision making, that is, adopting a neutral prior probability of 0.5 but leaving thresholds for decision making unchanged, coincides with Minimax decision making if multilocus DNA fingerprinting is employed.


Comparison of fingernail striation patterns in identical twins. The fingernail ridge patterns of a pair of identical twins were compared to each other, their parents, and an unrelated subject. The patterns of the twins' nails showed regions of strong similarity but were distinguishable from one another. Fewer similarities were found when comparing the nails to those of the parents and the unrelated control. The twins were shown to be monozygotic by means of DNA profiling. This therefore represents the first demonstration of unique fingernail ridge patterns in subjects shown conclusively to be identical twins. When the fingernail ridge patterns were examined with a scanning electron microscope, the backscattered electron (BEI) images were found to have superior contrast when compared to the secondary electron (SEI) images.


A statistical approach to drug sampling: a case study. In many countries it is left to the discretion of the court to accept or reject conclusions based on sampling procedures as applied to the total drug exhibit. As an alternative to this subjective approach, a statistical basis is presented using binomial and hypergeometric distributions to determine a lower limit for the proportion of units in a population which contains a drug, at a given confidence level. A method for calculating the total weight of a drug present in a population within a given confidence interval is also presented. In the event of no failures (all units sampled contain a drug), a sample size of six or seven units is generally sufficient to state that a proportion of at least 0.70 of the population contains a drug at a confidence level of at least 90%. When failures do occur in the sample, point estimation is used as the basis for selecting the appropriate sample size.


Ion mobility spectrometry of drugs of abuse in customs scenarios: concentration and temperature study. A custom-built ion mobility spectrometer has been used to obtain the IMS spectra of cocaine, heroin, amphetamine sulfate and LSD at different drug concentrations and desorption temperatures. Practical detection limits for these four drugs were obtained as a function of desorber temperature and for heroin as a function of analysis time. Spectral and ionization interferences for each of the four drugs of interest were determined. Spectral interferences by innocuous materials are few; ionization interferences occur only at very high ratios of the mass of innocuous material to that of the drug of interest.


Gunshot residue particles formed by using ammunitions that have mercury fulminate based primers. Ammunition having mercury fulminate-based primers are commonly manufactured by Eastern Bloc countries and used extensively in the Middle East. Gunshot residue (GSR) particles formed by firing these types of ammunition were examined. It was observed that much lower percentage of mercury-containing GSR particles were found in samples taken from a shooter as compared to the percentage of such particles in samples from cartridge cases. This fact must therefore be taken into account when interpreting case results. A plausible explanation for the results described is proposed.


Linguistic evidence indicative of authorship by a member of the deaf community. Documents authored by Deaf Americans were examined in order to determine if linguistic evidence indicative of this group of people is present. The native language of deaf people is not English, but rather American Sign Language (ASL). ASL is a visual-gestural language with its own principles of syntax. The evidence examined includes vocabulary, syntax, and word usage. Such characteristics are class evidence and are not a means of identification, but rather an investigative tool. Such information may be of assistance to the field investigator in either developing a suspect or limiting the number of initial suspects in a case. This research revealed that the use of ASL syntax and idioms and the problems associated with the use of English as a second language are indicative of authorship by a member of the Deaf Community. The results of this research will be of assistance to Document Examiners should they need to determine if a document was authored by a deaf individual.


Family violence as a determinant factor in juvenile maladjustment. The family is one of the major socialization agencies for children. Parents are one of the most important models from whom the child and adolescent acquire a wide variety of behavior patterns, attitudes, values, and norms. The aim of this study was to determine the importance of factors related to family conflicts in the genesis of social maladjustment. A total of 189 young people (110 boys and 79 girls) from training schools connected with the juvenile court in Murcia (Spain) were studied. The subjects' ages ranged from 11 to 18 years (mean 13.51, SD 0.16). Our sample comprised a group of minors who experienced a high incidence of intrafamilial pathology, which was found to be a significant discriminant factor. Aggressive behavior, rules, norms, values, opinions, and attitudes toward aggressivity can be learned in the family setting.


The application of immunoblotting to the phenotyping of haptoglobin. An immunoblotting method for phenotyping haptoglobin in serum and bloodstains has been developed. Haptoglobin isoproteins were separated by polyacrylamide gradient gel electrophoresis and then transferred to nitrocellulose by electroblotting. The use of 1 mm gels facilitated more rapid and effective transfer than conventional 3 mm thick gels. Nitrocellulose blots were developed by double antibody enzyme immunoassay. The detection limit for serum and bloodstains was improved 16 times compared to conventional staining using O-tolidine. The method could detect haptoglobin phenotypes from 0.001 microliter of whole blood. This detection limit is approximately 8 times lower than that of group specific-component analysis by immunoblotting.


Car surfing in Indiana--an unusual form of motor vehicle fatality. A new form of joyride known as "car surfing" with fatal results is documented. The possible role of this activity in extra-vehicular motor vehicle deaths involving teenage or youthful drivers is described. Potential scene and autopsy findings are discussed.


An unusual fatal case of accidental asphyxia in a child. The death of a three-year-old child by asphyctic mechanism is described. The child was accidentally suspended by the neck from a half-opened car window. This report details the form in which the accident occurred. The influence of the type of window and the autopsy findings.