[Amputation and exarticulation of the lesser toes]. / Amputation und Exartikulation der Kleinzehen.

OBJECTIVE: Amputations and exarticulations of the toes may be necessary due to several reasons. The goal is to remove necrosis or infection prior to its spread to the midfoot region. From a functional or cosmetic point of view, amputation/exarticulation of a single toe plays no major role. However, this can be different with exarticulation of several toes. INDICATIONS: Necrosis, trauma, infection, tumor, deformity. CONTRAINDICATIONS: Conditions where amputation/exarticulation of a toe is insufficient, e. g., in progressing peripheral arterial disease. SURGICAL TECHNIQUE: The toe can either be amputated through the distal phalanx or exarticulated in the metatarsophalangeal joint. POSTOPERATIVE MANAGEMENT: Orthopedic shoes or orthotic devices are rarely necessary when a single toe is amputated/exarticulated. However, concomitant deformities of the foot have to be thoroughly addressed. If more than one toe is amputated, silicone spacers may be necessary to prevent the remaining toes from deviating. RESULTS: Amputations and exarticulations of the toes are frequent and the procedure is technically simple. However, the complication rate is high due to typical indications making amputation necessary.

Intron retention as an alternative splice variant of the rat urocortin 1 gene.

Urocortin 1, highly conserved metazoan gene of the corticotropin-releasing hormone family, is a simple gene structured in two exons and the corresponding intron. The urocortin 1 prepropeptide is entirely coded in the second exon. Preliminary non-isotopic in situ hybridization experiments with an oligonucleotide complementary to an intron sequence of the urocortin 1 gene showed a significant cytoplasmic-like staining, suggesting the occurrence of an intron-retained urocortin 1 transcript. This observation prompted us to study whether the urocortin 1 gene presents alternative splicing by intron retention event. Confocal fluorescent in situ hybridization for urocortin 1 RNA and the use of the specific DNA dye TOPRO-3 allowed us to show significant expression of the intron-retained urocortin 1 transcript that did not colocalize with TOPRO-3 staining indicating a cytoplasmic localization for the intron-retained urocortin 1 transcript. The natural occurrence of a polyadenylated intron-retained urocortin 1 RNA was further documented by reverse transcriptase polymerase chain reaction (PCR), primed with oligo(dT), of total RNA extracted from three brain regions, a midbrain region containing the Edinger-Westphal nucleus, cerebellum and prefrontal cortex. In the three brain regions studied, it was possible to amplify both intron-less as well as intron-retained urocortin 1 transcripts. The use of PCR primers that simultaneously amplify both urocortin 1 transcripts allowed us to show that the expression of both urocortin 1 transcripts differs among the brain regions analyzed, suggesting a tissue specific regulation of this alternative splicing. In silico analysis of the five known mammalian urocortin 1 genomic sequences showed high conservation of the urocortin 1 intron sequence. Further studies should investigate the regulation of this intron retention event and its consequence for the functionality of the urocortin 1 gene.

8-oxoguanine DNA glycosylase, but not Kin17 protein, is translocated and differentially regulated by estrogens in rat brain cells.

8-oxoguanine DNA glycosylase and Kin17 are proteins widely distributed and phylogenetically conserved in the CNS. 8-oxoguanine DNA glycosylase is a DNA repair enzyme that excises 7,8-dihydro-8-oxoguanine present in DNA damaged by oxidative stress. Kin17 protein is involved in DNA repair and illegitimate recombination in eukaryotic cells. The present study evaluates the effect of ovarian hormones on the expression of both proteins in the magnocellular paraventricular nucleus of the hypothalamus and the bed nucleus of the stria terminalis in female and male rat brains. In the paraventricular nucleus, ovariectomy induced a significant decrease in the number of 8-oxoguanine DNA glycosylase-positive nuclei as well as in their relative fluorescent intensity as compared with ovariectomized-estradiol treated and proestrous groups. Confocal microscopy observation demonstrated that oxoguanine DNA glycosylase protein is located in the Hoechst-dyed nuclei and cytoplasm in male and ovariectomized rats. Surprisingly, following estradiol administration to ovariectomized and proestrous rats, the 8-oxoguanine DNA glycosylase immunolabeling was observed in the nucleolus, the cytoplasm and the dendrites of cells, while Kin17 protein was always localized in the cell nuclei. In the bed nucleus of the stria terminalis, the number of 8-oxoguanine DNA glycosylase-positive nuclei during proestrous was significantly lower than the number obtained in males and ovariectomized rats and similar to the number of ovariectomized-estradiol-treated groups. In contrast to these observations, no significant differences were observed in the expression of kin17 protein. Our results suggest that estrogens differentially regulate the expression of 8-oxoguanine DNA glycosylase, but not that of Kin17 protein, in specific regions of the rat brain and that estradiol can translocate the 8-oxoguanine DNA glycosylase protein within nuclei and to other subcellular compartments.

Chronic morphine treatment and withdrawal increase extracellular levels of norepinephrine in the rat bed nucleus of the stria terminalis.

Extracellular levels of norepinephrine (NE) and glutamate (Glu) in the ventral bed nucleus of the stria terminalis (vBNST) of saline- and chronic morphine-treated rats, with or without withdrawal, were studied by means of the in vivo microdialysis technique in anesthetized rats. In addition, the tissue concentration of NE was studied at different rostrocaudal levels of the vBNST. Chronic morphine treatment significantly increased extracellular levels of NE, but not Glu, in vBNST. At 48 h after naloxone-induced morphine withdrawal there was a further significant increase in the extracellular levels of NE, but not Glu, in vBNST. The presence of UK 14304, an alpha(2)-adrenergic agonist, induced a significant decrease in NE extracellular levels in all experimental groups. In contrast, UK 14304 induced a significant decrease in Glu extracellular levels only in saline-treated rats. The results also show that the vBNST presents a rostrocaudal gradient of NE and contains 9.4% of total brain NE. The increase in NE extracellular levels in vBNST induced by chronic morphine treatment and the further increase in NE levels 48 h after naloxone-induced morphine withdrawal suggest that NE in vBNST may be involved in the pharmacological effects of chronic morphine and withdrawal.

Medullary noradrenergic neurons projecting to the bed nucleus of the stria terminalis express mRNA for the NMDA-NR1 receptor.

The bed nucleus of the stria terminalis pars ventralis (vBNST) receives dense noradrenergic terminals and contains the highest concentration of noradrenaline (NA) in the brain. We used autoradiography following retrograde axonal transport of [(3)H]-NA to identify selectively whether noradrenergic neurons innervating the vBNST originate in the medulla oblongata and/or the locus coeruleus. In combination with this technique, non-isotopic in situ hybridization for the NMDA-NR1 receptor subunit mRNA was used to examine, on the same brain sections, its expression in noradrenergic neurons that innervate the vBNST. The results showed that 60 +/- 6% and 35 +/- 7% of the total number of radiolabeled cells detected after injection of [(3)H]-NA in the vBNST were located in brainstems A1 and A2 noradrenergic cell groups, respectively. In addition, 18.5 +/- 4.2% of radiolabeled cells in A1 and 15.7 +/- 5% in A2 also expressed the mRNA for the NMDA-NR1 receptor subunit. In contrast, only 4 +/- 3% of the radiolabeled cells were present in the locus coeruleus, and none of these cells was positive to NMDA-NR1 receptor subunit mRNA. The present results provide evidence that BNST noradrenergic fibers and terminals originate predominantly from A1 and A2 noradrenergic cell groups, and that a significant number of these noradrenergic neurons also express the mRNA for the NMDA-NR1 receptor subunit. The observation that brainstem noradrenergic neurons innervating the vBNST express NMDA receptor mRNA gives anatomical support to the regulation of NA release by NMDA presynaptic receptors.

[Parathyroid gland carcinoma with postoperative encephalopathy]. / Nebenschilddrüsencarcinom in Zusammenhang mit einem postoperativen Durchgangssyndrom.

We present a 78-year-old patient who suffered from symptomatic transitory psychotic syndrome after laparotomy. Persisting somnolence appeared with cardiopulmonary decompensation and gastrointestinal atony. Due to prolonged hypercalcemia primary hyperparathyreoidism was diagnosed. Resection of a large carcinoma of the parathyroids led to continuous clinical improvement.

Noradrenaline inhibits glutamate release in the rat bed nucleus of the stria terminalis: in vivo microdialysis studies.

The microdialysis technique was used to simultaneously study the in vivo extracellular levels of noradrenaline, glutamate, and gamma aminobutyric acid (GABA) in the bed nucleus of the stria terminalis in order to assess the regulation that noradrenaline may exert upon the release of amino acid neurotransmitters. Perfusion through the probe with UK14304, a selective alpha2-adrenergic agonist, produced a significant decrease of noradrenaline and glutamate extracellular levels. Perfusion through the probe with RX821002, a selective alpha2-adrenergic antagonist, produced a significant increase of noradrenaline and glutamate basal extracellular levels. Perfusion with prazosine, a selective alpha1-adrenergic antagonist, produced a significant decrease of noradrenaline basal extracellular levels without affecting glutamate levels. Under the same conditions, GABA basal extracellular levels were not changed in the presence of any of the alpha-adrenergic ligands studied. The perfusion of high potassium through the probe induced a significant Ca++dependent release of the three neurotransmitters; however, extracellular noradrenaline returned to normal levels even though potassium was still present. In addition, it was observed that alpha-adrenergic receptor ligands exerted differential effects upon K+-induced release of noradrenaline and glutamate. Perfusion with the nonselective alpha-adrenergic antagonist, phenoxybenzamine, presented a biphasic effect upon K+-induced release of noradrenaline; a significant decrease during the first 5 min of stimulation followed by a significant increase in the next 5 min of stimulation. Perfusion with RX821002 produced a significant increase in K+-induced release of noradrenaline that returned to normal basal values before the end of the stimulation period. In contrast, local perfusion with prazosine caused a significant decrease of K+-induced noradrenaline release. In the case of glutamate, perfusion through the probe with phenoxybenzamine produced a significant increase in K+-induced release of glutamate. In addition, RX821002 and prazosine produced a significant increase in K+-induced release of glutamate. Perfusion through the probe with UK14304 produced a significant decrease of both noradrenaline and glutamate K+-induced release. The present results show that noradrenaline in the bed nucleus of stria terminalis exerts a significant inhibition over its own release through alpha2-adrenergic receptors and over glutamate release mainly through alpha2-adrenergic receptors. Thus, the results suggest that noradrenaline in the bed nucleus of the stria terminalis maintains an inhibitory tone over the information flow mediated by glutamate.

Regulation of norepinephrine release from the rat bed nucleus of the stria terminalis: in vivo microdialysis studies.

The microdialysis technique was used to study the in vivo extracellular levels of norepinephrine in the bed nucleus of the stria terminalis. A basal level of 2.34 +/-0.25 fmol/microl of norepinephrine was observed. Desipramine (2 and 10 microM), a norepinephrine uptake blocker, significantly increased extracellular levels of norepinephrine. Reversed perfusion with high potassium in the presence of 2 microM desipramine induced the release of norepinephrine. Instead, in the presence of 10 microM desipramine, a significant decrease in the induced release of norepinephrine was observed. Clonidine, an alpha2-adrenergic agonist, significantly decreased basal extracellular levels of norepinephrine and the K+-induced release of norepinephrine. In contrast, yohimbine and RX821002, two alpha2-adrenergic antagonists, significantly increased basal extracellular levels of norepinephrine but not the release of norepinephrine induced by 70 mM K+. Perfusion of tetrodotoxin through the probe located in the bed nucleus of the stria terminalis significantly decreased both the basal extracellular level and the K+-induced release of norepinephrine. Furthermore, perfusion of tetrodotoxin through a microdialysis probe implanted in the medial forebrain bundle also decreased basal extracellular levels of norepinephrine in the bed nucleus of the stria terminalis. The results show that in vivo there is a significant noradrenergic tonic activity in the bed nucleus of the stria terminalis. This tonic activity depends on the impulse flow through medial forebrain bundle nerve fibers. Under these conditions, extracellular levels of norepinephrine in the bed nucleus of the stria terminalis are regulated by the magnitude of norepinephrine uptake and by presynaptic alpha2-adrenergic receptors.

Transport of nitric oxide synthase inhibitors through cationic amino acid carriers in human erythrocytes.

The interaction of arginine analogues, which are known to inhibit nitric oxide synthase, with two cationic amino acid transporters of human erythrocytes (systems y+ and y+L) was studied. Arginine and relevant analogues [NG-monomethyl-L-arginine (L-NMMA); NG-monomethyl-D-arginine (D-NMMA) and NG-nitro-L-arginine (L-NOARG)] were found to inhibit labeled lysine influx into intact erythrocytes. As expected, the pattern of inhibition reflected the contribution of the two distinct transport systems. All analogues showed a higher affinity for system y+L than for system y+. The half-saturation (inhibition) constants estimated for systems y+ and y+L (+/- SEM) were (microM): L-arginine, 55.7 +/- 5.4 and 2.4 +/- 0.1; L-NMMA, 151 +/- 13 and 7.5 +/- 0.5; D-NMMA, 2660 +/- 404 and 269 +/- 25; L-NOARG, 9414 +/- 169 and 594 +/- 35. The transport properties of the analogues were investigated using an assay based on the trans-stimulation of lysine efflux. The addition of saturating concentrations of unlabeled analogues to the external medium stimulated efflux of labeled lysine through systems y+L and y+, showing that the analogues can enter the cell through these pathways.

Regulation of endogenous noradrenaline release from the bed nucleus of stria terminalis.

The bed nucleus of stria terminalis (BNST) contains the highest concentration of noradrenaline (NA) in the brain. Minislices of the ventral portion of the bed nucleus of stria terminalis (vBNST) were used to study the release of endogenous NA. High K+ induced a Ca(2+)-dependent and reserpine-sensitive release of NA. Clonidine (1 microM), an alpha 2-noradrenergic receptor agonist, significantly decreased K(+)-induced release of NA, whereas yohimbine (1 microM), an alpha 2-noradrenergic antagonist, increased this release. N-Methyl-D-aspartate (NMDA), a specific agonist of NMDA-type glutamate receptors, evoked the release of NA from vBNST minislices. In the presence of D-serine (10 microM), an agonist at the glycine site associated with the NMDA receptor, the NMDA effect was significantly higher. Glycine (1 microM) also increased NA release evoked by NMDA. However, glycine exhibited a significant effect by itself, suggesting the existence of strychnine-sensitive glycine receptors in vBNST. Endogenous NA release induced by 40 mM K+ and NMDA was not additive. Thus, vBNST minislices seem to be a good model to study the release of endogenous NA in the CNS. Such NA release in the vBNST is regulated by alpha 2-noradrenergic receptors and by glutamate through NMDA receptors.

[Results of "expanded" arthrolysis of the knee joint]. / Ergebnisse "erweiterter" Kniegelenksarthrolysen.

This report shows the results of 20 patients, suffering on severe knee stiffness, who were treated between 1980-1989 at the Berufsgenossenschaftliche Unfallklinik in Tübingen with an expanded knee arthrolysis. The knee stiffness of all patients was caused by trauma (65% polytrauma) or infection. More than 2/3 of the patients (70%) had a preoperative degree of motion which was less than 60 degrees. In average 9 months after the initial trauma the expanded knee arthrolysis was performed. The arthrolysis was in most of the cases (n = 15) combined with a supracondylar correction osteotomy. The average preoperative range of motion from (ext./flex.) 0-15-62 degrees has postoperatively been increased to (ext./flex.) 0-5-92 degrees which corresponds to a relative improvement of motion of 43%. Eleven patients showed good or fair results. The prognosis of knee stiffness is influenced by the etiology, the pre-operative loss of motion and the period of time between initial trauma and arthrolysis, and as well by the intraoperatively achieved range of motion and the post-operative application of continuous passive motion. The expanded arthrolysis of the knee is a usefull instrument in the therapy of severe posttraumatic knee stiffness.

Studies of cholecystokinin in the rat bed nucleus of stria terminalis.

The release of cholecystokinin from the dorsal and ventral region of the rat bed nucleus of stria terminalis was studied. Minislices from both regions were superfused with Krebs-Ringer-phosphate, and the cholecystokinin released into the physiological medium was concentrated previous to radioimmunoassay determination. For this purpose, cholecystokinin was adsorbed onto a C18 reverse-phase column and eluted with acetonitrile. Cholecystokinin standards (10-50 pg) were subjected to the above procedure, which allowed a 20- to 50-fold concentration of the peptide with an 80% recovery. Potassium-induced release of cholecystokinin from minislices of dorsal and ventral regions of the bed nucleus of stria terminalis was measured successfully using the above procedure to concentrate the peptide. Lesion of the stria terminalis, a fiber tract originating in the amygdala, provoked a significant decrease in cholecystokinin levels in the ventral region of the bed nucleus of strial terminalis. Thus, cholecystokinin released from minislices of the ventral region of the stria terminalis may be of amygdaloid origin.

Differential effects of haloperidol on negative symptoms in drug-naive schizophrenic patients: effects on plasma homovanillic acid.

After 5 weeks of haloperidol, positive symptoms in drug-naive schizophrenic patients substantially subsided. Negative symptoms, although with a different temporal pattern, decreased after the fifth week of haloperidol treatment; specifically, a decrease was seen in anhedonia and affective flattening, whereas avolition-apathy and attentional impairment presented no changes. Alogia showed a decrease during the third week and a trend to return to placebo scores during weeks 4 and 5. Changes in affective flattening, alogia and attentional impairment correlated with changes in positive symptoms. During placebo, plasma homovanillic acid (HVA) correlated with negative symptoms and with changes presented by negative symptoms between the first and the fifth treatment week. These data show that negative symptoms respond differentially to neuroleptics and suggest that avolition-apathy may represent a different behavioral component of the schizophrenia process.

Non-neuronal endogenous GABA efflux from the rat oviduct.

The subcellular distribution of Gamma-aminobutyric acid (GABA) was studied in the rat oviduct. The highest content of GABA was found in the soluble fraction. The effect of chemical stimulation of the endogenous GABA efflux from the rat oviduct was examined. High K+ concentrations could not induce elevation of the GABA efflux. Instead, a continuous spontaneous GABA efflux without change for long periods of time was observed. The total GABA content and GABA concentration were determined in the rat oviduct on days 1, 5, 10, 15, 30, 35 and 40 of the postnatal period and also during the estrous cycle. During postnatal development the GABA levels increase gradually with time reaching at prepuberal age a concentration similar to that found in diestrous rats. In the estrous cycle both GABA content and GABA concentration reached the highest value in the proestrous and the lowest value in the estrous phase. These findings support the hypothesis that GABA efflux may be modulated by the changes in oviductal fluid volume during the estrous cycle.

Regulation of excitatory amino acid release by N-methyl-D-aspartate receptors in rat striatum: in vivo microdialysis studies.

The microdialysis technique was utilized to study the effects of N-methyl-D-aspartate (NMDA) receptor ligands on the in vivo release of endogenous glutamate (Glu) and aspartate (Asp) from the rat striatum. Addition of NMDA (250 and 500 microM) to the dialysis perfusion solution resulted in a striking dose-dependent increase in extracellular concentrations of Glu and Asp in the striatum. The NMDA-induced effects were reduced in a dose-related way by prior perfusion with 75 microM dizocilpine (MK-801), a non-competitive NMDA receptor antagonist. MK-801, at 75 microM, produced no changes on basal levels of Glu and Asp. However, 100 microM MK-801 did increase Glu and Asp extracellular concentrations. Local infusion with 500 microM D-serine, an agonist at the glycine site associated to the NMDA receptor, significantly increased basal level of Glu, but not Asp. Such D-serine-induced effects were reduced by 7-Cl-kynurenic acid (200 microM), a selective blocker of the glycine site present in the NMDA receptor. It is proposed that activation of NMDA receptors by endogenous Glu and Asp enhances the subsequent release of these excitatory amino acids in the striatum. Part of these NMDA receptors might be located presynaptically on cortico-striatal nerve endings. In addition, postsynaptic NMDA receptors present in the striatum may also indirectly modulate the release of Glu and Asp, through trans-synaptic mechanism.

Changes of norepinephrine levels and release in rat cerebral cortex during the estrous cycle.

We studied the influence of the estrous cycle and ovariectomy on the noradrenergic innervation of the rat cerebral cortex. The lowest norepinephrine (NE) concentration was found during estrus in frontal and occipital cortex. At that stage and at diestrus-2, 20 mM K+ induced the lowest release of [3H]NE from occipital region slices, and the highest release was found at 60 mM K+. Ovariectomy (7 days) decreased the 20 mM K+ effect. Yohimbine (10 x 10(-6) M) increased the induced NE release through the cycle but its effects disappeared after ovariectomy. In the frontal cortex the drug effect was only found at diestrus-1 and no changes were observed in the K+ effect through the cycle. Results suggest that normal endocrine influences can modify noradrenergic neurotransmission in the rat cerebral cortex.

[Arthrolysis as a surgical treatment concept of post-traumatic stiffness of the knee joint]. / Die Arthrolyse als operatives Behandlungskonzept der posttraumatischen Kniegelenksteifen.

In the period from 1977 to 1989 105 arthrolyses were performed in 102 patients. There were mainly posttraumatic fibroarthroses: 51 consecutive to fractures, 39 after ligamentous injuries, 13 post-infectious of which 11 were also post-traumatic and only 2 patients with rheumatological diseases. Remarkable is the increased number of fibroarthrosis after polytrauma (n = 26). The preoperative range of motion was under 30 degrees in 26 patients and 48 patients had a severely limited range of motions between 30 and 60 degrees. The follow-up examination performed in an average of 2 years after the operative mobilization showed that the initial mobility was more than doubled. These results are related to atiology, operative procedure and degree of severity of the preoperative stiffness. Fair to excellent results were obtained in almost 3/4 of the patients. We explain these results by an adapted extraarticular or combined procedure which were used in 63 cases. The open release is backed by an intensive rehabilitation program in which painlessness through PDA and an immediate postoperative continuous passive motion are of most importance.