Serotonergic function and late luteal phase dysphoric disorder

Thirty-eight subjects who met criteria for the DSM-III-R diagnosis late luteal phase dysphoric disorder (LLPDD) were compared with 18 controls in 5-HT uptake kinetics of the platelets in the premenstrual (day 26) as well as in the postmenstrual phase (day 4) of the cycle. Furthermore, 5-hydroxytryptophan (5-HTP) was administered to LLPDD patients and controls in both phases of the cycle, to investigate pituitary sensitivity for serotonin. Plasma samples for the measurement of cortisol and -endorphin were taken before and after oral administration of 200 mg 5-HTP, and considered as an index of pituitary-adrenal function. LLPDD was not associated with a lower platelet 5-HT uptake and content in the premenstrual phase of the cycle, compared with the postmenstrual phase. Patients appeared not to be different from controls in 5-HT uptake kinetics of platelets in the premenstrual phase of the cycle. No main differences were observed between LLPDD patients and controls in their ability to respond with secretion of cortisol and -endorphin to 5-HTP stimulation, either in the premenstrual, or in the postmenstrual phase. This observation could not be attributed to differences in 5-HTP metabolism. The findings of the present study do not support a specific role for 5-HT in the pathophysiology LLPDD.     

The Structure of Celiprolol

The crystal structure and nuclear magnetic resonance (NMR) spectra and assignments of celiprolol, N-[3-acetyl-4[3-[N-t-butylamino-2-hydroxypropoxy]phenyl]-N, N-diethylurea, are reported. Celiprolol crystallizes in the monoclinic space group, P2_l/a, with a = 9.081(2), b = 13.800(4), and c = 17.471(5) Å and = 95.04(2)°. Structure was solved by direct methods; structure refinement to R of 0.058. Intermolecular hydrogen-bonding in the crystal is discussed. The ¹H, ¹³C, and two-dimensional (2D) NMR spectra of the hydrochloride have been obtained and definitive signal assignments made.     

Client typology based on functioning level assessments: utility for service planning and monitoring

Cluster analysis was used to develop a six-group typology based on level of functioning data from 2,447 clients with serious mental illness served by the Michigan public mental health system. The groups are described in terms of level of functioning in 16 domains, global functioning, diagnosis, demographic characteristics and services used. A group of older, poor functioning clients with high health needs was identified. A second group of highly dysfunctional clients with few health needs was also found. Two groups of young adult "chronic" clients were found: one with extensive substance abuse problems and one with moderate substance abuse problems and extreme levels of suicidal and aggressive behavior. Two groups of relatively good functioning clients were also identified: one with some problems in many areas and a second with functional problems in a number of life areas and pronounced symptoms of depression and demoralization. The results point to the utility of cluster analysis as a mechanism to organize and identify patterns within the rich array of information provided by multidimensional level of functioning assessments. The uses of empirically derived client types in planning and monitoring mental health services are discussed.     

Extensive metallosis and necrosis in failed prostheses with cemented titanium-alloy stems and ceramic heads

We describe three prostheses with cemented titanium-alloy stems and Al2O3 ceramic femoral heads which had to be revised after a mean period of implantation of 78 months. In each case, the neck of the prosthesis had been so severely worn that the profile was elliptical rather than circular. There was severe metallosis of the periprosthetic tissues. Metal particles isolated from the tissues were approximately one nanometre in size and the ratios of titanium, aluminium and vanadium in the particles were the same as in the original alloy. Histologically, the high concentration of metal particles masked the presence of high-density polyethylene (HDP) debris, but again particles about one nanometre in size were isolated from the tissues. The severe necrobiosis and necrosis noted were consistent with other reports of the presence of extensive wear particles in periprosthetic tissues. Wear is presumed to have occurred as a result of mismatch between the shape or size of the taper cone and the femoral head, or to changes in the geometry of loading due to migration of the cup. To facilitate early intervention, patients with this design of prosthesis should be monitored radiologically.     

DNA methylation changes in multiple myeloma.

Using a candidate gene approach, we analyzed the methylation status of the promoter-associated CpG islands of 11 well-characterized tumor suppressor genes by methylation-specific polymerase chain reaction in five multiple myeloma (MM) cell lines and 56 patients with malignant plasma cell disorders. The frequency of aberrant methylation among the patient samples was 46.4% for SOCS-1, 35.7% for p16, 21.4% for E-cadherin, 12.5% for DAP kinase and p73, 1.8% for p15, MGMT as well as RARbeta, and 0% for TIMP-3, RASSF1A and hMLH1. We found at least one hypermethylated gene in 80.4% of the primary patient samples, while 33.9% harbored two or more hypermethylated genes. For the first time, we show that p73 may be hypermethylated in MM and thus be involved in the pathogenesis of plasma cell disorders. Hypermethylation of p16 at diagnosis was associated with a poorer prognosis. In patients with plasma cell leukemia, we found frequent simultaneous hypermethylation of p16, E-cadherin and DAP kinase. We conclude that aberrant methylation of tumor suppressor genes is a common event in malignant plasma cell disorders and that there is a correlation between methylation patterns and clinical characteristics in MM patients.     

Abrogated energy-dependent uptake of cisplatin in a cisplatin-resistant subline of the human ovarian cancer cell line IGROV-1

The parental IGROV-1 human ovarian adenocarcinoma cell line was intermittently exposed to increasing concentrations of cisplatin to obtain resistant sublines. A stable resistant subline with a resistance factor of 8.4 had been developed after 9 months and 28 passages, which was denoted IGROV_CDDP. A high correlation coefficient of 0.97 was found between the log cell survival and the DNA-adduct peak level during the process of resistance development. IGROV_CDDP was strongly cross-resistant to carboplatin and doxorubicin and moderately cross-resistant to etoposide, docetaxel, and topotecan. Only minor resistance against 5-fluorouracil was observed, whereas IGROV_CDDP was not cross-resistant to methotrexate. Intracellular accumulation of cisplatin was 65% lower in IGROV_CDDP as compared with parental IGROV-1 at 37  °C under normal conditions. Coincubation of cisplatin with the Na⁺/K⁺-ATPase inhibitor ouabain resulted in a more pronounced decrease in platinum accumulation in IGROV-1 (44% decrease) than in IGROV_CDDP (26% decrease). Under energy-depleting conditions the accumulation of cisplatin in the parental cell line was approximately 60% lower than that observed under normal (energy [i.e., ATP] rich) culture conditions. In contrast, the accumulation in IGROV_CDDP was not affected by ATP-depletion. There appeared to be no significant difference between the intracellular accumulation of platinum in the resistant and sensitive cells under conditions of energy deprivation or when the uptake was studied at 0  °C. In conclusion, abrogation of energy-dependent accumulation in IGROV_CDDP seems to be a major mechanism of resistance to cisplatin in this cell line. Received: 21 January 1997 / Accepted: 22 July 1997     

Combinedin vitro effect of marijuana and retrovirus on the activity of mouse natural killer cells

Both marijuana and retroviruses impair natural killer (NK) cell functions, but no data on their simulataneous effects are available. Similarities to human AIDS induced by Friend leukemia complex (FLO and its helper Rowson-Parr virus (RPV) provides a mouse model to study drug-virus action. Leukemia susceptible BALB/c and resistant C57BL/6 mice were infected, then at time intervals their nylon wool-separated splenocytes were exposed to tetrahydrocannabinol (THC) for 3h. Natural killer cell activity against Yac-1 cells was assayed by 51Cr-release for 4 and 18h. Recovery of splenocytes was found to be suppressed by FLC, but in BALB/c only by RPV. After a transient enhancement in C57BL/6 by FLC, NK cell activity of both mice became suppressed early (2 to 4 days), normalized subsequently and enhanced late (11 to 14 days) postinfection. A moderate increase in BALB/c, no change in C57BL/6 were induced by low (1-2.5 g/ml) THC doses. NK cell activity of BALB/c became suppressed exponentially by higher (5-10 g/ ml) THC doses in 18h as compared to 4h assays, while its proportional and moderate impairment was seen in C57BL/6. The magnitude of NK cell activity of infected mice was determined by THC: enhancement or impairment followed those of untreated, infected counterparts on the level of THC-treated cells. Low doses hardly, high doses additively influenced NK cells of infected BALB/c. THC slightly affected very early and late enhancement in NK cell activity of FLC infected C57BL/6, but augmented RPV induced suppression late in 18h assays. Genetic factors similar to endotoxin resistance, altered cytokine profile might determine these effects. Similar phenomena in humans might result in earlier manifestation of AIDS.     

Patient Capacity in Mental Health Care: Legal Overview

The discriminatory effects of categorizing psychiatric patients into competent and incompetent, have urged lawyers, philosophers and health care professionals to seek a functional approach to capacity assessment. Dutch and English law have produced some guidelines concerning this issue. So far, most legal systems under investigation have concentrated on alternatives for informed consent by the patient in case of mental incapacity, notably substitute decision-making, intervention of a judge and advance directives. It is hard to judge the way in which the law may further adapt to a more functional assessment of capacity, because the nature of law shows that legal reforms usually take place only when new methods have been accepted by the field. This is not yet the case today.