Diagnosis of schizophrenia by computer and clinicians: A pilot study

Investigations show significant disagreement among mental health professionals in diagnosing schizophrenia.^1–11 Recently, computer-based systems have been used in attempts to improve diagnostic consistency. Spitzer and Endicott, among others, have devised a computer program using the Mental Status Examination Report (MSER) as input data.^12–19 The MSER is a systematic, relatively objective inventory of observed behaviors used to obtain a mental status. The MSER was used at the Hillside Division during 1973 and 1974. It was filled out 1 week after admission by therapists who were specially trained for this task. It was noted that a nonschizophrenic computer diagnosis was given to a number of patients diagnosed schizophrenic by clinicians, but the reverse rarely occurred. Was this due to the computer program, the MSER, clinicians, or other factors? These questions have heightened relevance in light of the imminence of Professional Standards Review Organization (PSRO).²⁰ Hospitals may be required to establish definitive operational diagnostic criteria and correlated treatments in order to maintain accreditation and be reimbursed by third-party payers. This study investigated these diagnostic discrepancies in order to ascertain what specific criteria could be used in making a schizophrenic diagnosis in hospitalized patients. Secondarily, the study sought to shed further light on whether such a computer system could be useful as an adjunctive diagnostic modality to pinpoint difficult cases.     

Examination of the failure properties of the anterior cruciate ligament during the estrous cycle

The purpose of this study was to determine whether the mechanical properties of the rat anterior cruciate ligament (ACL) vary when tested in vitro at different stages of the estrous cycle. Sixty female rats were allocated to four groups according to their stage of the estrous cycle: diestrus (n=16), proestrus (n=17), estrus (n=13) and metestrus (n=14). Right hindlimbs were harvested for mechanical testing and left hindlimbs were harvested for immunohistochemical staining to confirm the presence of the estrogen receptor. Results from the first relaxation test showed a significant difference between the estrus and proestrus stage, which was not observed in a second subsequent relaxation test. Likewise, no significant differences were found when comparing failure load and stiffness between the different stages of the estrous cycle. These results suggest that normal physiological fluctuations in estrogen during the estrous cycle did not alter the failure properties of the rat ACL.     

Stress-induced enhancement of fear learning: an animal model of posttraumatic stress disorder

Fear is an adaptive response that initiates defensive behavior to protect animals and humans from danger. However, anxiety disorders, such as Posttraumatic Stress Disorder (PTSD), can occur when fear is inappropriately regulated. Fear conditioning can be used to study aspects of PTSD, and we have developed a model in which pre-exposure to a stressor of repeated footshock enhances conditional fear responding to a single context-shock pairing. The experiments in this chapter address interpretations of this effect including generalization and summation or fear, inflation, and altered pain sensitivity. The results of these experiments lead to the conclusion that pre-exposure to shock sensitizes conditional fear responding to similar less intense stressors. This sensitization effect resists exposure therapy (extinction) and amnestic (NMDA antagonist) treatment. The pattern predicts why in PTSD patients, mild stressors cause reactions more appropriate for the original traumatic stressor and why new fears are so readily formed in these patients. This model can facilitate the study of neurobiological mechanisms underlying sensitization of responses observed in PTSD.     

Association of progesterone receptor polymorphism with recurrent abortions

OBJECTIVE: The current study sought for polymorphisms within the progesterone receptor (PR) gene. Allele and genotype frequencies of patients with repeated abortions were compared to a control group. DESIGN: All exons of the PR of 42 women with repeated abortions and 40 controls were screened for single nucleotide polymorphisms (SNP). Determination of the DNA-sequences was performed. RESULTS: Three SNPs were detected (exon 1: G1031C Ser344Thr; exon 4: G1978T Leu660Val, exon 5: C2310T His770His). These SNPs are linked. The more frequent wildtype (*1) allele and the rarer (*2) allele were found in the control group and in the study group at different frequencies (control group: *1/*1: 78%, *1/*2: 22%, *2/*2: 0%; patient group: *1/*1: 50%, *1/*2: 43%, *2/*2: 7%). The genotypes distributions differed significantly from each other (P=0.019, chi2=7.879). CONCLUSIONS: The data suggest that the rarer PR allele may be associated with an increased likelihood of repeated miscarriages contributing to its multi-factorial causes.     

Pathogenesis and treatment of neoplastic diseases of the papilla of Vater: Kausch-Whipple procedure with lymph node dissection in cancer of the papilla of Vater

Cancer of the papilla or the ampulla of Vater appears, from a clinical point of view, to be an intraduodenal or ampullary cancer. An adenoma-dysplasia-carcinoma sequence has been established. In 20%–40% of the patients with an adenoma of the papilla, a cancerous lesion in the adenoma is additionally observed. Oncological resection using a Kausch-Whipple technique or a pylorus-preserving partial pancreatico-duodenectomy (PPPD) offers a 5-year survival probability of between 45% and 65%. The hospital mortality after oncological resection at experienced centers is below 5%. The most frequent treatment-related complication is pancreatic fistula, which occurs in around 20% of the patients. In about 10% of the patients with a pT₁ cancer and in 25% to 67% with pT₂ and pT₃ cancer, lymph node involvement has been observed. Lymph nodes in front of and behind the head of the pancreas are the primary targets for cancer cell disseminations. In more than one-third of the patients, lymph nodes in the inter-aortocaval space and the lymph nodes around the superior mesenteric artery and the nodes in the pancreatic segment of the hepatoduodenal ligament are involved. Therefore, tissue dissection, including, selectively, the N₂ lymph nodes, is an essential component of radical surgery for cancer of the papilla. A standard Kausch-Whipple resection or PPPD without a selective extended lymph node dissection, including the interaortocaval and superior mesenteric artery nodes, results in about 30% of the patients having an R₂-resection, i.e., with cancer left behind. The long-term survival is determined by the tumor biological factors: (1) absence of lymph node involvement and (2) absence of infiltration into the pancreas. The surgeons contribution to the cure of cancer of the papilla is to perform an R₀-resection with low hospital mortality and low postoperative morbidity. Patients without lymph node involvement, and with absence of infiltration into the pancreas, no lymph vessel invasion, and tumor-negative margins have major benefits from oncological resection in regard to curability of the cancer.     

Surfactant in newborn compared with adolescent pigs: adaptation to neonatal respiration

Surfactant composition and function differ between vertebrates, depending on pulmonary anatomy and respiratory physiology. Because pulmonary development in pigs is similar to that in humans, we investigated surface tension function, composition of phospholipid molecular species, and concentrations of surfactant protein (SP)-A to -D in term newborn pigs (NP) compared with adolescent pigs (AP), using the pulsating bubble surfactometer, mass spectrometry, high-performance liquid chromatography, and immunoblot techniques (IT). NP was more potent than AP surfactant in reaching minimal surface tension values near zero mN/m. Whereas SP-A and SP-D were comparable, SP-B and SP-C were increased 3- to 4-fold in NP surfactant. Moreover, fluidizing phospholipids such as palmitoylmyristoyl-PC (PC16:0/14:0) and palmitoylpalmitoleoyl-PC (PC16:0/16:1) were increased at the expense of PC16:0/16:0 (32.4 +/- 0.6 versus 44.5 +/- 3.2%, respectively). Whereas concentrations of total anionic phospholipids were similar in NP and AP surfactant (9.9 +/- 0.3 and 12.0 +/- 0.3%, respectively), phosphatidylinositol was the predominant anionic phospholipid in NP surfactant. We conclude that, compared with AP, NP surfactant displays better surface tension function under dynamic conditions, which is associated with increased concentrations of SP-B and SP-C, as well as fluidizing phospholipids at the expense of PC16:0/16:0.     

CYP2D6 genotype: impact on adverse effects and nonresponse during treatment with antidepressants-a pilot study

OBJECTIVE: Treatment with antidepressants is frequently associated with adverse effects or insufficient clinical response. Several antidepressants are metabolized by cytochrome P450 (CYP) 2D6. The activity of this enzyme markedly varies among individuals from poor to ultrarapid metabolism on the basis of the polymorphism of the CYP2D6 gene. This association study investigated whether the CYP2D6 genotype distribution differs from that of the German white population either in patients with marked adverse effects or in nonresponders during treatment with antidepressants metabolized by CYP2D6. METHODS: By use of a retrospective, naturalistic approach, outpatient practices and hospitals in southern Germany were asked to report on patients who either had had adverse drug effects or were nonresponsive during treatment with CYP2D6-dependent antidepressants. CYP2D6 genotyping was performed by a panel of polymerase chain reaction techniques. Poor and intermediate metabolizer alleles, as well as allelic duplications of CYP2D6, were detected. RESULTS: Of 28 patients with adverse effects during treatment with a CYP2D6-dependent antidepressant, 8 (29%) had 2 inactive alleles and thus were poor metabolizers. This is a 4-fold increase as compared with the German population (P <.0001). Amplification of fully functional alleles (associated with ultrarapid metabolism) was found in 3 (19%) of the 16 nonresponders (approximately 5.0-fold higher in nonresponders than in the population) (P =.0012). CONCLUSION: The results suggest that the CYP2D6 genotype is associated with the occurrence of adverse effects and clinical nonresponse in psychiatric patients treated with CYP2D6-dependent antidepressants.     

Molecular species compositions of lung and pancreas phospholipids in the cftr(tm1HGU/tm1HGU) cystic fibrosis mouse

Fatty acid analysis of phospholipid compositions of lung and pancreas cells from a cystic fibrosis transmembrane regulator (CFTR) negative mouse (cftr(-/-))suggested that a decreased concentration of docosahexaenoate (22:6(n-3)) and increased arachidonate (20:4(n-6)) may be related to the disease process in cystic fibrosis (CF). Consequently, we have determined compositions of the major phospholipids of lung, pancreas, liver, and plasma from a different mouse model of CF, the cftr(tm1HGU/tm1HGU) mouse, compared with ZTM:MF-1 control mice. Electrospray ionization mass spectrometry permitted the quantification of all of the individual molecular species of phosphatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn), phosphatidylglycerol (PtdGly), phosphatidylserine (PtdSer), and phosphatidylinositol (PtdIns). There was no deficiency of 22:6(n-3) in any phospholipid class from lung, pancreas, or liver from mice with the cftr(tm1HGU/tm1HGU). Instead, the concentration of 20:4(n-6) was significantly decreased in plasma PtdCho species and in pancreas and lung species of PtdEtn, PtdSer, and PtdIns. These results demonstrate the variability of membrane phospholipid compositions in different mouse models of CF and suggest that in cftr(tm1HGU/tm1HGU) mice, the apparent deficiency was of 20:4n-6- rather than of 22:6n-3-containing phospholipid species. They highlight a need for detailed phospholipid molecular species analysis of cells expressing mutant CFTR from children with CF before the therapeutic effects of administering high doses of 22:6(n-3)-containing oils to children with CF can be fully evaluated.     

Single motor unit analysis from spatially filtered surface electromyogram signals. Part 2: Conduction velocity estimation

The aim of the study was to compare experimentally conduction velocity (CV) estimates obtained with different estimation methods based on surface electromyogram (EMG) signals detected using five spatial filters. The filters investigated were the longitudinal single and double differential, transverse single and double differential, and normal double differential. The same surface EMG signals detected as described in Part 1 were used in this work. CV was estimated with four commonly used delay estimation techniques, i.e. from the distance between the peak values of two waveforms (with and without polynomial interpolation around the peak), and by the maximum likelihood estimate (MLE) based on two or more surface EMG channels. The average standard deviation of CV estimation (for all the MUs and the two muscles together) was 0.61 ms⁻¹ and 0.79 ms⁻¹ for the peak method, with and without interpolation, respectively, and 0.50ms⁻¹ and 0.31 ms⁻¹ for the MLE method, from two and more surface EMG channels, respectively. Moreover, the mean of CV estimates varied by as much as 1 ms⁻¹ depending on the spatial filter used and the method adopted for CV estimation. Considering the dependence on the spatial filter only, the average (over all estimation methods) CV estimates obtained with the five spatial filters were 4.32 ms⁻¹ (normal double differential), 4.23ms⁻¹ (longitudinal double differential), 4.61 ms⁻¹ (transverse double differential), 4.64ms⁻¹ (transverse single differential) and 4.03 ms⁻¹ (longitudinal single differential). It was concluded that the comparison of single MU CV values obtained in different studies is critical if different spatial filters and processing techniques are used for their estimation. Higher estimates of CV were attributed to a smaller reduction in non-travelling signal components and thus were assumed to be positively biased.     

Surface detected potentials of normal and reinnervated motor units: a simulation study for muscles consisted of short fibres

We aimed to check whether the characteristics used up to now in macro EMG to distinguish between normal and reinnervated motor unit potentials (MUPs), were suitable for surface detected MUPs. MUPs produced by normal and reinnervated MUs were simulated with a fast and precise convolution model. An increased number of fibres in the MU territory enhanced the amplitude, area and RMS of the MUP proportionally irrespective of the MU-electrode distance. An increased scatter of the end-plates and greater desynchronization in the fibres' activation decreased the MUP amplitude and affected the temporal characteristics of the MUP (duration of the negative phase and its area to amplitude ratio). The effects were more pronounced at shorter distances. At larger distances, the effect of the MU-electrode distance on temporal and amplitude characteristics of MUPs was much stronger than that of the parameters changed with reinnervation. We conclude that reinnervated MUs consisting of short fibres can not be distinguished from the normal ones by means of characteristics of MUP used in macro EMG. To discriminate reinnervated MUs non-invasively, the MUP amplitude should be normalized in respect of the MU-electrode distance or other MUP characteristics (independent of MU-electrode distance and sensitive to reinnervation) should be used.