[Parkinson's Disease at the Border Between Inpatient and Outpatient Care]. / Das idiopathische Parkinson-Syndrom an der Grenze von ambulanter zu stationärer Versorgung.

Parkinson's disease is characterized by a continuous spectrum of varying severity. The treatment is driven by new and sometimes highly complex therapeutic procedures. These two aspects are responsible for the blurred dividing line between outpatient and inpatient care. The aim of this article is to define criteria that should help determine the indication for inpatient or outpatient treatment. We introduce quality requirements that have already been taken into account in part in therapy modalities such as Parkinson complex treatment. The decision on the appropriate form of care affects the medical freedom of therapy, which must reconcile the legitimate interest of patients to receive optimal care with the given economic conditions. Our aim is to provide guidance on decisions on the best form of treatment in the context of changing framework conditions in the health sector.

Oligoarray (105K) CGH analysis of chromosome microdeletions within 10q22.1q24.32.

To populate the chromosome 10 genetic landscape with clinical correlations we describe 3 non-overlapping, nearly contiguous deletions within chromosome 10q22.1q24.32. Three cases were studied by oligoarray comparative genomic hybridization (CGH), cytogenetics, and/or fluorescence in situ hybridization. The array CGH showed de novo deletions: arr 10q22.1q22.2(74,115,795-77,077,025)×1dn, arr 10q22.3q23.2(81,437,039-89,144,374)×1dn and arr 10q23.33q24.32(94,894,780-103,144,781)×1dn. Developmental delay, speech impairment and growth retardation were observed in all 3 patients. Facial palsy and renal dysplasia were the other notable findings. The renal dysplasia was ascribed to the loss of a PAX2 gene in the 10q23.33q24.32 deletion patient (OMIM *167409). The facial palsy was seen in the case with a deletion of 10q22.1q22.2. One of three 10q22.3q23.2 deletions involved low copy repeats. We have described the phenotype specific to the chromosome region involved within 10q22.1-q24.32. The oligoarray analysis improved the clinical management of the patients and enabled counseling for deleted genes.

Evidence for mouse Th1- and Th2-like helper T cells in vivo. Selective reduction of Th1-like cells after total lymphoid irradiation.

Purified CD4+ BALB/c spleen T cells obtained 4-6 wk after total lymphoid irradiation (TLI) helped normal syngeneic B cells to produce a vigorous antibody response to TNP keyhole limpet hemocyanin in adoptive cell transfer experiments. However, the same cells failed to transfer delayed-type hypersensitivity to the adoptive hosts as measured by a foot pad swelling assay. In addition, purified CD4+ cells from TLI-treated mice were unable to induce graft vs. host disease in lethally irradiated allogeneic C57BL/Ka recipient mice. In response to mitogen stimulation, unfractionated spleen cells obtained from TLI mice secreted normal levels of IL-4 and IL-5, but markedly reduced levels of IL-2 and INF-gamma. A total of 229 CD4+ clones from spleen cells of both normal and TLI-treated mice were established, and the cytokine secretion pattern from each clone was analyzed. The results demonstrate that the ratio of Th1- and Th2-like clones in the spleens of normal BALB/c mice is 1:0.6, whereas the ratio in TLI mice is approximately 1:7. These results suggest that Th2-like cells recover rapidly (at approximately 4-6 wk) after TLI treatment and account for the early return of antibody helper activity and secretion of IL-4 and IL-5, but Th1-like cells recover more slowly (in approximately 3 mo) after irradiation, and this accounts for the deficit in cell-mediated immunity and the reduced amount of IL-2 and IFN-gamma secretion.

Natural killer lines and clones with apparent antigen specificity.

Fresh CD3-, CD16+ lymphocytes that adhered to selected allogeneic lymphoblastoid cell lines (LCL) were cultured with LCL in the presence of IL-2-containing medium. The resulting lines as well as clones derived from these lines expressed CD16 and/or CD56, but lacked detectable CD3 or TCR-alpha/beta or TCR-gamma/delta complexes on the cell surface. Northern blot analysis failed to detect CD3 epsilon or TCR-beta transcripts, but revealed the presence of a TCR-gamma chain transcript in one of these lines. In addition to displaying potent cytolytic activity against K562 erythroleukemia cells (a classical NK target), the vast majority of these lines and clones lysed their specific stimulator LCL to a significantly greater extent than irrelevant LCL. This selective killing was inhibited by the addition of cold stimulator LCL or K562 cells, or anti-LFA 1 mAbs, but not by irrelevant LCL or mAbs to CD3, class I or class II MHC antigens. These results indicate that some CD3- lymphocytes, phenotypically indistinguishable from NK cells, can recognize and lyse allogeneic targets in a specific manner.

Telomeres cluster de novo before the initiation of synapsis: a three-dimensional spatial analysis of telomere positions before and during meiotic prophase.

We have analyzed the progressive changes in the spatial distribution of telomeres during meiosis using three-dimensional, high resolution fluorescence microscopy. Fixed meiotic cells of maize (Zea mays L.) were subjected to in situ hybridization under conditions that preserved chromosome structure, allowing identification of stage-dependent changes in telomere arrangements. We found that nuclei at the last somatic prophase before meiosis exhibit a nonrandom, polarized chromosome organization resulting in a loose grouping of telomeres. Quantitative measurements on the spatial arrangements of telomeres revealed that, as cells passed through premeiotic interphase and into leptotene, there was an increase in the frequency of large telomere-to-telomere distances and a decrease in the bias toward peripheral localization of telomeres. By leptotene, there was no obvious evidence of telomere grouping, and the large, singular nucleolus was internally located, nearly concentric with the nucleus. At the end of leptotene, telomeres clustered de novo at the nuclear periphery, coincident with a displacement of the nucleolus to one side. The telomere cluster persisted throughout zygotene and into early pachytene. The nucleolus was adjacent to the cluster at zygotene. At the pachytene stage, telomeres rearranged again by dispersing throughout the nuclear periphery. The stage-dependent changes in telomere arrangements are suggestive of specific, active telomere-associated motility processes with meiotic functions. Thus, the formation of the cluster itself is an early event in the nuclear reorganizations associated with meiosis and may reflect a control point in the initiation of synapsis or crossing over.

Regional lung function in patients with bronchial asthma.

The regional distribution of pulmonary ventilation and perfusion and regional alveolar ventilation/perfusion ratios were measured with radioactive xenon ((133)xenon) in 10 patients with asthma in remission. Four subjects had normal ventilation distribution, four had hypoventilation in some regions and normal ventilation in others, and two patients had abnormal ventilation in almost all lung regions. The lung bases were involved most frequently and the middle zones least frequently. Correlation was good between the degree of over-all ventilatory impairment calculated from (133)xenon values and measurement of the maximal midexpiratory flow rate the same day. Regions which were hypoventilated had low ventilation/perfusion ratios and also tended to be hypoperfused. In the eight subjects who had been studied similarly 5 yr previously, changes in regional function correlated in general with changes in over-all function.

Acylglycerol reactivity and reaction mechanism of bovine milk lipoprotein lipase.

The sequential lipolysis of trioleoylglycerol and the triacylglycerols of very-low-density lipoprotein by bovine milk lipoprotein lipase can be described by the consecutive reactions: (formula: see text) where k'1, k'2 and k'3 are apparent first-order rate constants. The values of these rate constants dictate several conclusions concerning the reaction mechanism of this enzyme. The significant differences in the k'1, k'2 and k'3 values for trioleoylglycerol substrate imply that cleavage of the acyl-enzyme intermediate is not the rate-limiting step of the overall lipolysis reaction. This conclusion is further supported by the lack of an effect of hydroxylamine on the reaction rate. In addition, the observed isotope effect of k1 (H2O): k1(D2O) of 1.32 with trioleoylglycerol substrate suggests that the acyl-enzyme formation may contribute to the rate-limiting step of the lipoprotein-lipase-catalyzed reaction. In the presence of excess bovine serum albumin, the transfer of fatty acid product from the enzyme to albumin must be fast, since the k'1 values are not dependent on albumin concentration. When albumin is not in excess, the reaction is retarded and the study of reaction kinetics demonstrates negligible reaction after the available albumin is saturated.

Effect of estrogen on triacylglycerol metabolism: inhibtion of post-heparin plasma lipoprotein lipase by phosvitin, an estrogen-induced protein.

PIP: The effects of phosvitin and lipovittelin on partially purified postheparin plasma levels of lipoprotein lipase (LPL) and triacylglycerol (TGL) and adipose tissue LPL were studied in laying and nonlaying female turkeys and estrogen-treated male turkeys. Postheparin plasma lipolytic activities and those of LPL and TGL decreased 2- to 3-fold after the onset of egg production, while a 24-fold increase in triacylglycerol (TG) was observed. Lipovittelin had no effect on either TGL or LPL, while phosvitin, in a dose of 3 mcg protein/ml assay mixture, had a strong inhibitory effect on plasma LPL and chicken adipose tissue LPL. TGL was not affected by phosvitin. The results suggest that phosvitin may have a role in the regulation of adipose tissue and plasma levels of TG in laying birds.^ieng

Eleven lymphoid phenotypic markers in HIV infection: selective changes induced by zidovudine treatment.

HIV infection induces substantial changes in the expression of many lymphocyte phenotypic markers as well as depletion of CD4 lymphocyte numbers. A comprehensive study was undertaken to determine whether seven lymphocyte phenotypic changes associated with HIV infection (increased CD38, HLA-DR, CD57, and CD71 and decreased CD11b, CD45RA, and leu-8) are altered by zidovudine (ZDV) administration. Levels of the four major lymphoid subsets (CD4, CD8, B, and NK cells) and changes in the serum activation markers neopterin and beta 2-microglobulin (beta 2M) were also measured. Elevated pretreatment expression of CD38 and CD71 was reduced significantly toward normal at 2 weeks by ZDV; however, CD38 and CD71 returned to pretreatment levels at different rates. The kinetics of CD38 reduction and the return to pretreatment levels were similar to those of serum neopterin and beta 2M. HLA-DR decreased in many but not all subjects. CD4 lymphocytes showed a transient increase, most evident at 8 weeks of treatment. Lymphoid phenotypes that did not show significant changes after ZDV therapy included CD57, CD11b, CD45RA, and leu-8 markers as well as CD8 T cells, CD20 B cells, and CD56 NK cells. The fact that some lymphocyte phenotypic markers change toward normal with ZDV treatment and others do not indicates that complex processes underlie immune perturbations of HIV infection. Several phenotypic markers (CD38, CD71, and HLA-DR) that are susceptible to short-term effects of ZDV (but with changes that differ from CD4 T cell changes) are surrogate marker candidates for evaluation in anti-HIV treatment.

The effect of zidovudine treatment on serum neopterin and beta 2-microglobulin levels in mildly symptomatic, HIV type 1 seropositive individuals.

Sixty-one subjects with mildly symptomatic human immunodeficiency virus (HIV) infection were included in a double-blind, randomized, placebo-controlled trial of zidovudine (part of AIDS Clinical Trials Group protocol 016, ACTG 016) to evaluate changes in the serum immune activation markers neopterin and beta 2-microglobulin (beta 2M) as early markers of the antiviral effect of zidovudine on HIV type 1 (HIV-1) infection. The mean values of serum neopterin and beta 2M levels in 27 placebo-treated subjects tended to increase with time. The mean value of neopterin in 34 subjects receiving zidovudine decreased at 4 weeks (15.76 nmol/L before treatment to 12.73 nmol/L, p = 0.001). The maximum reduction was seen at 8 weeks of treatment (10.78 nmol/L, p less than 0.0001). Subsequently, the mean value of serum neopterin increased but remained below the pretreatment value for more than a year. Serum beta 2M levels decreased (from 3.01 to 2.69 mg/L at 4 weeks, p = 0.01) and reached the lowest level at 8 weeks (2.45 mg/L, p = 0.0002) in zidovudine recipients. The mean beta 2M level returned to pretreatment value at approximately 24 weeks of the treatment. There was a close correlation between changes from baseline in serum neopterin and beta 2M during the first 16 weeks of the zidovudine therapy, but not later. Subjects with greater reductions of serum neopterin or beta 2M tended to maintain lower levels of these markers with continued zidovudine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Michelin tire baby syndrome: familial constriction bands during infancy and early childhood in four generations.

We report on an infant with an unusual pattern of transitory familial constriction bands distributed symmetrically and circumferentially over the neck, forearms, and lower legs. Family history showed the occurrence of similar bands among individuals in 4 generations transmitted as an autosomal dominant trait. Neck and limb distribution in the other affected family members was also symmetrical and circumferential, with spontaneous resolution taking place during childhood. This case represents another example of the Michelin tire baby syndrome, also known as multiple benign circumferential skin creases of the limbs, and further demonstrates its autosomal dominant mode of inheritance.

Is decreased activity of C-II activated lipoprotein lipase in type III hyperlipoproteinemia (broad-beta-disease) a cause or an effect of increased apolipoprotein E levels?

Apolipoprotein E (ApoE; "arginine-rich" polypeptide) strongly inhibited both C-I and C-II activated lipoprotein lipases but not the protamine insensitive triglyceride lipase. Inhibition of lipoprotein lipases by ApoE in contrast to inhibition by C-III was not reversed to any significant extent by either increased concentration of activator or triglyceride in the substrate. Our previous studies have shown that in a type III hyperlipoproteinemia (broad-beta-disease) a post-heparin plasma lipoprotein lipase activated by C-II polypeptide of lipoprotein C is decreased in enzyme activity and exhibits an impaired ability to hydrolyze triglycerides in very low density lipoproteins. Type III patients are characterized by elevated concentrations of ApoE in the serum. The data presented in this report suggest that the decreased C-II activated lipoprotein lipase may be further aggravated by increased ApoE levels. Since this enzyme is involved in the catabolism and removal of lipoproteins, decreased activity of C-II activativated lipoprotein lipase may presumably be responsible for increased ApoE.

Evaluation of the Short Parkinson's Evaluation Scale: a new friendly scale for the evaluation of Parkinson's disease in clinical drug trials.

The extensive use of the Unified Parkinson's Disease Rating Scale (UPDRS) has revealed low interrater reliability in some items and redundancy in others. In view of these shortcomings, we have structured a new scale that includes a zero-to three-point scale for each item in the evaluation of PD. The mental axis includes memory, thought disorders, and depression. Activities of daily living (ADL) includes eight items: speech, eating, feeding, dressing, hygiene, handwriting, walking, and turning in bed. The motor examination includes eight items: speech, tremor, rest and posture, rigidity, finger tapping, arising from chair, gait, and postural stability. Complications of therapy were also included: dyskinesias, dystonia, motor fluctuations, and freezing episodes, collected by history. In addition, a global scoring for motor fluctuations that should complement the Hoehn and Yahr Scale was incorporated. In this report, we present a statistical analysis of the ADL, motor evaluation, and complications of therapy sections. Concerning the interrater reliability mean, Kendall's W values were >0.9 for most of the items in the Short Parkinson's Evaluation Scale (SPES). Kendall's W <0.8 (motor evaluation) was found for two items of the SPES and nine items of the UPDRS. The mean interrater reliability for both scales across all seven centers (seven Kendall's W for seven centers) (Mann-Whitney test) showed no statistical differences between the scales. Spearman's correlations between items of both scales were significant. Factor analysis of the SPES and UPDRS data revealed a four-factor solution that explained approximately 60% of the data. All participating centers found the SPES easier to apply and quicker to complete, when compared with the UPDRS. The results obtained strongly favor the introduction of SPES for clinical practice.

In vitro excystment of the metacercariae of Cloacitrema michiganensis (Trematoda: Philophthalmidae).

In vitro excystment studies on the metacercariae of Cloacitrema michiganensis indicated that optimal excystment occurred when the cysts were incubated in a complete medium containing trypsin and bile salts at a temperature of 41 to 42 C and a pH of 7.8 in the absence of acid pretreatment. A relatively lower percentage of excystment was obtained following pretreatment with acidified pepsin or Hanks' balanced salt solution (BSS). A low percentage of inactive worms excysted when the cysts were incubated in: trypsin after pretreatment with acidified pepsin; bile salts following pretreatment with acidified pepsin; and the complete medium, after acid pretreatment followed by the reductant (sodium dithionite). Treatment with bile salts after pretreatment with acidified Hanks' BSS, the reductant and the complete medium, and simple media such as Hanks' BSS and warm physiological saline resulted in no excystment. The in vitro excystment process involves two phases, activation and emergence, which are initiated by the metacercaria in response to the appropriate conditions. It is suggested that a synergistic effect between trypsin and bile salts is necessary for excystment whereas acid pretreatment is not.

The life cycle of Cloacitrema michiganensis McIntosh, 1938 (Trematoda: Philophthalmidae).

Experimental infections of Cloacitrema michiganensis were established in chicks by inoculation per cloaca with excysted metacercariae. Ovigerous adults were present 20 days later with eggs containing ocellate miracidia after 21 days. The eggs hatch in utero; the miracidium contains a fully developed redia. Rediae of 2 size groups were present in the digestive gland of the brackish-water snail, Cerithidea californica. Megalurous cercariae are released and encyst on submerged objects. The stages of C. michiganensis resembled those of Parorchis acanthus, a philophthalmid also infecting C. californica, except for differences in the epidermal plate count of their miracidia and in their cercarial stage which was larger in P. acanthus and had a spinuous tegument with a collar of spines.

Osteopathia striata syndrome. Clinical, genetic and radiologic considerations.

Osteopathia striata, an autosomal dominant disorder, has been diagnosed in a 19-year-old mildly retarded woman. In addition, she has macrocephaly, a leonine facies, disfigurement of the lower jaw, a cleft palate and mixed hearing loss. Roentgenograms of the skull and long bones show thickening of the calvarium, particularly at the base, mandibular hyperplasia, and striations in the long bones and pelvis. Except for the cleft palate, which has not been previously reported, and the retardation, which appears to be quite uncommon in this condition, these findings are characteristic of osteopathia striata. Because the disorder may resemble several other conditions, the differential diagnosis should include osteopoikilosis, the autosomal dominant form of osteopetrosis, and hyperostosis corticalis generalisata.