An ultrasound approach to the posterior compartment and anorectal dysfunction.

INTRODUCTION AND HYPOTHESIS: Patients with anorectal dysfunction are common and can be quite challenging to diagnose. The common underlying causes for such conditions are usually anatomical in nature, which may be difficult to fully evaluate by clinical examination alone. The aim of this video was to demonstrate how multicompartmental ultrasound imaging can be utilized clinically in the evaluation of patients with anorectal dysfunction. METHODS: Pertinent ultrasound findings of the common anatomical causes of defecatory dysfunction were discussed in this video. RESULTS: Different ultrasound techniques were shown. CONCLUSION: In conclusion, multicompartmental ultrasound imaging is an easy, cost-efficient, and valuable tool in the evaluation of patients with anorectal dysfunction.

A randomized trial of the effects of coached vs uncoached maternal pushing during the second stage of labor on postpartum pelvic floor structure and function.

OBJECTIVE: The purpose of this study was to determine if refraining from coached pushing during the second stage of labor affects postpartum urogynecologic measures of pelvic floor structure and function. STUDY DESIGN: Nulliparous women at term were randomized to coached (n = 67) vs uncoached (n = 61) pushing. At 3 months' postpartum women underwent urodynamic testing, pelvic organ prolapse examination (POPQ), and pelvic floor neuromuscular assessment. RESULTS: Urodynamic testing revealed decreased bladder capacity (427 mL vs 482 mL, P = .051) and decreased first urge to void (160 mL vs 202 mL, P = .025) in the coached group. Detrusor overactivity increased 2-fold in the coached group (16% vs 8%), although this difference was not statistically significant (P = .17). Urodynamic stress incontinence was diagnosed in the coached group in 11/67 (16%) vs 7/61 (12%) in the uncoached group (P = .42). CONCLUSION: Coached pushing in the second stage of labor significantly affected urodynamic indices, and was associated with a trend towards increased detrusor overactivity.

The safety of reusing injectable collagen: a multicenter microbiological study.

We have previously reported pilot data regarding the safety of saving partially used syringes of a glutaraldehyde cross-linked collagen for use in subsequent treatment sessions with the same individual. That single institution study involved 56 partially used syringes cultured for aerobic bacteria. Only one weakly positive culture was detected among these 56 samples, which prompted us to carry out this expanded study involving multiple centers and different injection techniques. Samples were collected from four centers. Following periurethral injection in an office setting, 166 partially used syringes of glutaraldehyde cross-linked collagen were refrigerated for between 1 and 104 weeks (average 58). Material from all 166 syringes was then cultured qualitatively and quantitatively for both aerobic and anaerobic organisms. Collagen from one syringe grew >100,000 colonies of Escherichia coli. All other cultures were negative. In the pilot study, one culture of 56 syringes was weakly positive for coagulase-negative staphylococcus. When the results from both studies were considered together, only two of 222 partially used syringes (0.9%) were contaminated. The background risk of local infection associated with periurethral collagen injection is approximately 0.29%. Using the statistical equation 'number needed to harm', we found that a clinician would have to reuse 111 syringes at a saving of $34,965 before he or she would cause a single local injection by so doing. Therefore, we feel that it may be cost-effective and safe to reinject material from a partially used syringe of glutaraldehyde cross-linked collagen during a subsequent treatment session on an individual.

Correlation of symptoms with location and severity of pelvic organ prolapse.

OBJECTIVE: The purpose of this study was to compare the symptoms that are related to pelvic floor dysfunction with the location and severity of the coexisting prolapse. STUDY DESIGN: Two hundred thirty-seven consecutive patients with symptomatic pelvic organ prolapse came to Johns Hopkins Medicine during a 24-month period beginning in July 1998 and completed a symptom-specific Likert scale questionnaire that included standardized questions that were compiled from commonly used validated instruments. All questionnaires were completed by the patients before they were seen by a physician. Further evaluation included a standardized physical examination that included the International Continence Society's system for grading uterovaginal prolapse. Symptoms were categorized according to both severity and associated anatomic compartment. Symptoms that were related to urinary and anal incontinence and voiding, defecatory, sexual, and pelvic floor dysfunction were analyzed with respect to location and severity of pelvic organ prolapse with the use of the nonparametric correlation coefficient, Kendall's tau-b. RESULTS: The mean age of the women was 57.2 years (range, 23-93 years); 109 of the women (46%) had undergone hysterectomy. Overall, stage II was the most common pelvic organ prolapse (51%) that was encountered. In 77 patients (33%), anterior compartment pelvic organ prolapse predominated; 46 patients (19%) demonstrated posterior compartment prolapse, whereas 26 patients (11%) had apical prolapse. In 88 patients (37%), no single location was more severe than another. Voiding dysfunction that was characterized by urinary hesitancy, prolonged or intermittent flow, and a need to change position was associated with the increasing severity of anterior and apical pelvic organ prolapse. Pelvic pressure and discomfort along with visualization of prolapse were strongly associated with worsening stages of pelvic organ prolapse in all compartments. Defecatory dysfunction characterized by incomplete evacuation and digital manipulation was associated with worsening posterior compartment pelvic organ prolapse. Impairment of sexual relations and duration of abstinence were strongly associated with worsening pelvic organ prolapse. An inverse correlation was observed between increasing severity of pelvic organ prolapse and urinary incontinence and enuresis. CONCLUSION: Women with pelvic organ prolapse experience symptoms that do not necessarily correlate with compartment-specific defects. Increasing severity of pelvic organ prolapse is weakly to moderately associated with several specific symptoms that are related to urinary incontinence and voiding, defecatory, and sexual dysfunction.

Influence of ethanol on metabolism of methamphetamine in rats including hair analysis.

To investigate possible influences of ethanol (EtOH) on metabolism of methamphetamine (MA), dark agouti (DA) rats were assigned to 3 groups including EtOH mono-dosing group, MA mono-dosing group and combined dosing group of EtOH and MA. Following successive administration of respective drugs, time-course changes of plasma and urine levels of EtOH and its metabolites, as well as alterations of plasma, urine, hair levels of the MA and its metabolites, were monitored. Preliminary hydrolysis of the glucuronate conjugates was required because parahydroxymethamphetamine (p-OHMA) and parahydroxyamphetamine (p-OHAP) were promptly conjugated with glucuronic acid in the body. When compared with EtOH group, the maximum plasma concentration of EtOH occurred with some delay in EtOH + MA group, suggesting possibility of some delay of its metabolism. MA concentrations in EtOH + MA group were slightly higher until 6 hours after administration when EtOH was detectable in the blood whereas concentrations of amphetamine (AP) in EtOH + MA group were less, on the contrary. Concentrations of p-OHMA and p-OHAP were obviously less in EtOH + MA group. These findings indicate that N-demethylation and parahydroxylation of aromatic ring of MA would be inhibited in the presence of EtOH. Concentrations of MA and AP in hair were higher in EtOH + MA group. Not only difference in AUC but also possible increase in uptake of the drugs into hair could likely account for this phenomenon.

Effects of human papillomavirus-associated cells on human immunodeficiency virus gene expression.

OBJECTIVE: To examine the effects of soluble factors secreted by human papillomavirus (HPV)-associated cells on human immunodeficiency virus (HIV) expression. METHODS: Supernatants collected from cultured cervical biopsies and cervical cancer cell lines, and HPV-immortalized and normal keratinocytes were tested for the ability to induce HIV p24 production in two cell lines that contained latent HIV (the U1 monocytic line and the ACH-2 T cell line). Levels of HIV p24 were measured by enzyme-linked immunosorbent assay (ELISA). Culture supernatants were also assayed for the inflammatory cytokines interleukin 6, tumor necrosis factor, and interleukin 1 beta by ELISA. RESULTS: Supernatants from all epithelial cells tested upregulated HIV p24 expression in the U1 line but not in the ACH-2 cells. Only differentiated normal keratinocytes induced p24 production by ACH-2 cells. Neutralization of the cytokines, particularly interleukin 6, partially reduced the level of HIV-inducing activity in the culture supernatants. Additionally, cervical biopsies from HIV-infected women cultured in vitro also were able to induce HIV in U1 cells but not ACH-2 cells. CONCLUSIONS: Our results suggest that HPV infection of the cervix might influence HIV pathogenesis by inducing the production of immune and inflammatory factors that enhance HIV expression.

[Histological study of early postmortem changes in various organs: comparison of the paraffin embedding method and the epoxy resin embedding method].

For the purpose of morphological assessment of the early postmortem interval, Wistar rats were killed by cervical dislocation and left at 23 degrees C for 1, 3, 5, 10, 15 and 24 hours. After a given postmortem interval, tissue samples taken from kidney, pancreas, liver, heart and skeletal muscle were embedded in paraffin or epoxy resin and examined by light microscopy. Specimens obtained from the paraffin block did not show a good correlation between histological changes and postmortem interval, because the postmortem changes continued during the fixation period. On the other hand, the time course of histological changes in specimens obtained from the epoxy block, particularly the development of clumping of nuclear chromatin and cytoplasmic vacuolation in each organ, reflected the postmortem interval because of the rapid fixation by glutaraldehyde. These histological changes were characteristic of each organ up to 24 hours after death. In addition, the semithin epoxy resin section made high-resolution light microscopy possible. Therefore, the epoxy resin embedding method is superior to the paraffin embedding method for the purpose of estimation of the time of death. The morphological changes characterising time after death are as follows: at 1 hour after death, cytoplasmic vacuolization and slight clumping of nuclear chromatin in pancreatic acinar cells; at 3 hours after death, slight clumping of nuclear chromatin in distal tubules, cytoplasmic vacuolization in skeletal muscle, and edema in cardiac muscle; at 5 hours after death, clumping of nuclear chromatin in proximal tubules as well as distal tubules, and cytoplasmic vacuolization in hepatocytes; at 10 hours after death, edema in proximal tubules, condensation of nuclear chromatin (apoptosis) and edema in distal tubules, and atrophy of acinar cells in the pancreas; at 15 hours after death, cytolysis of distal tubules; at 24 hours after death, cytolysis of hepatocytes and clumping of chromatin in skeletal muscle. Thus we can conclude that the time course of histological changes is useful for the estimation of postmortem interval.

Light and electron microscopic immunocytochemistry on the localization of 17 alpha-hydroxylase/C17,20-lyase (P450c17) in the rat placenta.

The rat placenta is the primary source of androgens during the second half of pregnancy. Androgens are converted to estrogens in the ovaries and contribute to the maintenance of normal pregnancy. We immunocytochemically characterized the cellular and subcellular localization of cytochrome P450 of 17 alpha-hydroxylase/C 17,20-lyase (P450c17), an enzyme responsible for androgen synthesis, in the rat placenta. We also observed the fine structure of the placenta by electron microscopy. The rat placenta had a different structure from the primate, and contained four zones: labyrinth, basal zone, decidua basalis, and metrial gland. The labyrinth had three trophoblastic layers and fetal endothelium, and P450c17 immunoreactivity was homogeneously localized in the three trophoblastic layers but not in the fetal endothelium. In the basal zone, various types of trophoblasts were observed, and the immunoreaction was localized in small basophilic cells and giant cells. The intensity of staining was heterogeneous among these cells. The decidua basalis showed no immunostaining. Subcellular localization of the enzyme was in the cytoplasm, but not in the nucleus or mitochondria. The present study demonstrated a steroidogenic potency in both the labyrinth and the basal zone, although it was shown only in the basal zone in previous studies.

Urinalysis of body packers in Japan.

Urinalysis was performed on nine body packers/smugglers who were referred to the emergency room of a hospital near the New Tokyo International Airport between September 1994 and February 1996. This analysis had rarely been used on suspected body packers in Japan. Only one of the nine body packers was a female. Foreign bodies were detected in the gastrointestinal tracts of the body packers by plain x-ray photography or computerized tomography, and the suspected drugs were cocaine (five cases), heroin (two cases), opiate (one case), and marijuana (one case). The results of urinalysis and confessions of the smugglers corresponded well for the latter three drugs (four cases). In two of the suspicious cocaine cases, opiates were detected along with cocaine by urinalysis, and the metabolites were confirmed by gas chromatography-mass spectrometry. The urinary screening tests of another two suspicious cocaine cases were negative. Opiates (morphine and codeine), but no cocaine metabolites, were detected in the urine of the subject who confessed to smuggling in cocaine only. It may be inferred from these results that urinalysis on body packers is beneficial to both the patient (body packer) and the physician in preventing the disastrous outcome of drug intoxication. It can also be concluded that there is a need for the prompt establishment of a protocol that includes urinalysis upon admission to the hospital for the management of body packers in Japan.

[An investigation of drug abuse and the utility of toxicology screening for use in emergency centers].

The results of toxicology screening of samples from 725 patients admitted to the Critical Care Medical Center (CCMC) of Nippon Medical School during a 10-month period from 1992-1993 (Group A) and a 4-month period from 1995-1996 (Group B) were discussed. We investigated the drug use of emergency patients using immunoassay. EMIT and Triage. The results were confirmed by Gas Chromatography/Mass Spectrometry (GC/MS). Blood samples were analyzed for ethanol (EtOH) by head space gas chromatography. Overall, 18% of the 725 cases tested positive for drugs, 13% for EtOH. Recently the positive rates of drugs and EtOH have been increasing. The positive rates for drugs in Group A and Group B were 15% and 23%, and EtOH were 11% and 17%, respectively. False positive cases caused by the cross-reactivity to analog were found in both EMIT and Triage. But the reliability of both methods was sufficient for clinical use. Rapid in easy toxicology screening can provide useful clinical information for patients admitted to a CCMC, especially for patients who have been injured, have sustained unknown-etiology consciousness disturbances, have CPAOA (Cardio Pulmonary Arrest on Arrival) or have committed drug abuse. We conclude that toxicology screening using immunoassay methods is suitable for use in an emergency center.

[Histopathological study on acute poisoning of methamphetamine, morphine or cocaine].

Methamphetamine, morphine or cocaine was injected intraperitoneally into Wistar rats (male, 6 weeks old) at a dose of 50 mg/kg, 125 mg/kg, or 50 mg/kg body weight, respectively. These doses of drugs were determined to ensure that the rats would show signs of drug intoxication and survive for a day. Over the period from 5 min to 18 hr after injection, concentrations of the drugs and metabolites in blood were analyzed by the GC/MS method, and the histopathological changes of the heart, lungs, liver and kidneys were examined by light microscopy. The time of maximum drug concentration in the blood after injection was 5 min in the methamphetamine-treated group, 1 hr (total morphine) in the morphine group and 5 min in the cocaine group. These blood concentrations decreased with time. In the liver at 2.5 hr after injection of methamphetamine, centrolobular vacuolation and diffuse eosinophilic changes of hepatocytes appeared. At 6 hr this damage spread to the midzone of the liver and partial necrosis of the centrolobe was found. At 18 hr the liver damage became worse and necrosis was also found in the midzone of the liver. In the heart, from 2.5 hr, eosinophilic changes of the myocardium were observed diffusely. Furthermore, at 18 hr, partial inflammatory cell infiltration and contraction bands were observed. The degree of histopathological damage did not coincide with the time of maximum drug concentration. In the morphine group, centrolobular and midzonal vacuolation, diffuse fatty degeneration and eosinophilic changes were observed in the liver from 2.5 hr to 18 hr after the administration. No necrosis was found, perhaps because the rats did not suffer the hyperthermia observed in the methamphetamine group. The degree of histopathological damage became more serious with time, as it did in the methamphetamine group. In the cocaine group, no histopathological changes were observed, probably because the doses of cocaine were too small to cause histopathological damage, and because cocaine is more rapidly metabolized than methamphetamine or morphine. These results suggest that in histopathological investigations necessitated by drug intoxication, measuring drug concentrations in the blood might be useful in determining the causes of histopathological changes more clearly.

Primate rod and cone photoreceptors may differ in glucose accessibility.

PURPOSE: Glucose is crucial for the function of retinal photoreceptors, other retinal neurons, and glial cells. Exogenous glucose can be extracted from the retinal and choroidal circulation, and endogenous glucose may be generated from breakdown of intracellular glycogen stores. Because glucose deprivation is a critical component of retinal ischemia, the authors sought to determine the sites of glucose entry into and generation within the retina. METHODS: The localization of the glucose transporter, GluT-1, and the brain and muscle isozymes of glycogen phosphorylase, GlyP, was studied by immunohistochemistry of adult human and monkey retinas. RESULTS: Brain glycogen phosphorylase (B-GlyP) immunoreactivity was found in cone, but not rod, photoreceptors. There was immunostaining of foveal and peripheral cones throughout the cytoplasm from the outer segment to the synaptic pedicle. Short wavelength ("blue") cones were positive for B-GlyP. Diffuse staining of the inner and outer plexiform and the nerve fiber layers did not resemble the distinct morphology of Müller cells. Immunoreactivity to muscle GlyP (M-GlyP) was confined to selected synaptic layers of the inner plexiform layer in monkey retina. Staining with antibody to GluT-1 demonstrated diffuse reactivity throughout the retina, including the blood-retinal barrier cells, retinal pigment epithelium, and vascular endothelium. Ultrastructural immunohistochemistry showed staining of rod and cone inner and outer segments. CONCLUSIONS: These immunohistochemical studies indicate that rod and cone photoreceptors have the biochemical capability to transport exogenous glucose from the circulation. Only cones appear capable of using endogenous glycogen stores. These findings imply that cones could be more resistant to acute reductions in circulating glucose during hypoglycemia. However, during hypoxic insult, glycogenolysis and anaerobic glycolysis could result in increased production of intracellular lactic acid, potentially predisposing the cone to acidotic damage.

MRI and MRS studies on acute effects of ethanol in the rat brain.

Magnetic resonance imaging and spectroscopy (MRI and MRS) were used to examine the effects of intoxicating doses of ethanol on the rat brain. 1H-MR images were obtained using three different methods: (1) PD weighted images, (2) T1 weighted images and (3) T2 weighted images. T1 and T2 relaxation times of the tissues were calculated by pixel-to-pixel image computation. After ethanol treatment, the cerebral hemispheres showed high signal intensities in the T1 weighted images, whereas low signal intensities were observed in the T2 weighted images, markedly in the cortex. At 4 h, the T1 values significantly decreased in the thalamus and the hypothalamus of the ethanol treated rats compared with those of the animals under pentobarbital anesthesia. At 1 h, the T2 values significantly decreased in the cortex of the ethanol treated rats. At 4 and 24 h, the T2 values significantly decreased throughout the cerebral hemispheres in the ethanol treated rats. The in vivo 31P-MRS results showed that after ethanol treatment, ATP and phosphocreatine slightly decreased, but not to a great degree. Intracellular pH levels, determined using the values of the chemical shift in inorganic phosphate peaks, decreased and returned to normal by 4 h. In the highly sedated animals, the acidosis observed early on was followed by heavy alkalosis. In in vitro 1H-MR spectra of brain and blood extract samples, many kinds of metabolites were assigned. The quantitative results were as follows: (1) Blood and brain ethanol levels rose to a peak at 1 h after ethanol treatment and no ethanol was detected at 24 h in any samples. (2) Blood acetate levels increased significantly, and returned to the control level by 24 h, whereas the brain acetate levels were largely unchanged. (3) Blood lactate levels decreased significantly at 0.5 h and brain lactate levels mildly increased and rose to a peak at 2 h. (4) Brain N-acetylaspartic acid (NAA) increased at 0.5 h significantly and decreased significantly at 4 h. Electron microscopic findings were as follows: (1) Both neuronal and glial cells were edematous after ethanol treatment. (2) Congestion was serious in all the regions we observed, and it was still present 24 h after ethanol treatment. (3) Swelling of mitochondria was observed in capillary endothelial cells. Our results suggest that high doses of ethanol cause circulatory disorders in the rat brain and disturb the water balance in the cerebral tissues, changing the structures of intracellular water molecules. It also causes metabolic confusion without depletion of high energy phosphate metabolites.

[The effect of flumazenil administration on acute cocaine intoxication of rats].

Flumazenil was studied on cocaine intoxicated rats for its preventive effect on seizure, death and loss of righting reflex. Two minutes after the intraperitoneal injection of cocaine (70 mg/kg) into a rat, flumazenil and diazepam were administered at the clinically corresponding dose intraperitoneally. Flumazenil at a dose 0.125 mg/kg extended the onset time of the cocaine induced seizure. Flumazenil at 0.5 or 1.0 mg/kg with diazepam 2.0 mg/kg, prevented the seizure, and kept righting reflex. It was observed that use of flumazenil in combination with cocaine had the effect of the benzodiazepine receptor.

[Ultrastructural changes of liver, heart, lung and kidney of mice in a large dose of ethanol injection].

Ethanol was injected intraperitoneally to dd-strain mice (20-25 g) with a dose of 5 g/kg body weight. The animals were sacrificed by the cervical dislocation at 4, 8, 12 and 24 hr after the ethanol injection. The changes of the ultrastructure of liver, heart, lung and kidney were examined by a transmission electron microscope. The results; from 4 hr to 24 hr after ethanol injection, deposition of fat droplets, swelling of mitochondria, enlargement of rough endoplasmic reticulum and loss of glycogen granules were observed in hepatocytes. Also, the edema of hepatocytes and intravascular hemostasis were found. These changes were aggravated with time course. In the heart, intravascular hemostasis, edema of myocardium, remarkable decrease of glycogen, swelling of mitochondria and appearance of I bands of myocardial fibers were observed. The damage to the myocardium by ethanol injection was similar to that associated with ischemia and anoxia. In the lung and the kidney, at early time after ethanol injection intravascular hemostasis and cell edema were observed but no other electron microscopical changes were found during the experiment. At 4 hr and 24hr after ethanol injection the edema of sinusoidal endothelial cell of liver and at 24hr that of endothelial cell of capillaries of heart were observed. These histological results suggest that the cell damages and intravascular hemostasis would be caused mainly by a direct action of ethanol. The damages of the liver and the heart, however, on the time blood ethanol was not detected would be caused by the disturbance of metabolism owing to ethanol oxidation.

[Death investigation system in the United States].

In light of recent developments and public interest on the issue of organ transplant and the definition of death by neurological function ("brain death"). A more expansive role of medicolegal investigation of deaths may be needed. This article was presented for the purpose of understanding the medicolegal investigative system in the United States. The traditional coroner system in the United States was taken from the English system and was established as an elected coroner system during a colonial period. The coroner system became more politically involved and the coroner was elected by popular votes. The political aspect was the main driving force and the medicolegal aspect was ignored, thus, the Commonwealth of Massachusetts was the first state to adopt the medical examiner system. In 1991, 41 out of 50 states have adopted the medical examiner system, either state-wide or on a local option. One of the principal differences between coroner and medical examiner systems is the qualification of the head of the agency. The coroner is an elected individual who acts as an administrator and conducts quasi-judicial function of the department. The medical function is delegated to a physician who performs his duty often on a part-time basis. The medical examiner's office is headed by a Board certified Forensic Pathologist who acts as an administrator and directs all functions including medical and scientific investigation. He is a public employee and is protected under the civil service rules, thus, his decision would be less likely influenced by political pressure. The jurisdiction of the coroner and medical examiner is generally the same by law, however a medical examiner's approach and decision-making is more medically oriented and tends to be more expansive and ready to adopt to the needs in medicolegal issues arising from scientific progress.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of pars planitis with cryotherapy.

Cryotherapy was performed on 28 eyes exhibiting massive exudates (snowbank) over the pars plana and the ora serrata. Twenty-six patients ranging in age from 8 to 52 years were treated and then followed up for a median of 34 months. Eleven eyes needed repeat cryotherapy. After cryotherapy, retinal vasculitis and vitreous opacities decreased in most eyes. Although only 3 of 5 eyes with a snowbank greater than 90 degrees and treated over 1 year from the onset achieved visual acuity of 20/25 or better, all 12 eyes with a snowbank smaller than 60 degrees and treated within 3 months after the onset maintained a visual acuity of 20/25 or better. The prognosis was not different from the 20 eyes that received systemic steroid treatment and the 8 eyes that received no systemic steroids. We recommend cryotherapy as the primary treatment for pars planitis with a snowbank.

Application of a computer-assisted high-performance liquid chromatographic multi-wavelength ultraviolet detection system to simultaneous toxicological drug analyses.

An emergency drug screening system for the separation and identification of toxic drugs, MULTI-HPLC, is presented. Chromatographic peaks, which were impossible to identify with a conventional high-performance liquid chromatographic UV detection system, became distinguishable by the spectral search and retention prediction of the data-processing program MCASYST. Sixty-five toxic drugs, frequently identified in drug poisionings in Japan, were selected as references in the drug library. Retention time, optimum detection wavelength, detection limit and recoveries from serum and urine were listed. Possible applications of the system are demonstrated, using gastric contents, sera and urines in cases of multiple drug ingestion. Quantitative analysis was sufficiently sensitive and precise to permit clinical diagnosis with increased accuracy.