Risk factors of violent offending in mentally ill prisoners with autism spectrum disorders.

BACKGROUND: Results of research regarding a possible causal relation between autism spectrum disorders (ASDs) and violence are mixed. Several explanations have been proposed. AIMS: To assess prevalence rates of comorbid disorders in a large sample of mentally ill offenders diagnosed with ASD. Offenders with and without comorbid mental disorders were compared on several characteristics. To better understand the relationship between ASD and violent criminal behavior, the predictive value of several proposed risk factors (comorbidity, negative social network/influenceability, and childhood trauma/victimization) on violent offending was investigated. METHOD: Data of 394 male offenders with a diagnosis of ASD were included. Prevalence rates of comorbid mental disorders next to ASD were calculated, and characteristics were compared using chi-square or t-tests. The predictive value of the risk factors was assessed using a binary logistic regression (n = 357). RESULTS: High rates of comorbidity were found (78.9%), specifically for substance use disorders (39.8%), schizophrenia spectrum disorders (31.7%), and neurodevelopmental disorder other than ASD (24.1%). Offenders with and without comorbidity differed significantly in their criminal and mental health care history. Both comorbidity (OR = 1.68; 95% CI 1.27-2.18) and a negative social network/influenceability (OR = 1.49; 95% CI 1.11-1.99) showed to be significant predictors of violent offending within this sample. CONCLUSIONS: The highest rates of comorbid disorders found were disorders that have been previously linked to violent offending, and the risk of violent offending could be unrelated to ASD. However, the role of social functioning indicates a risk specific to the symptoms of ASD.

Scimitar syndrome; an unusual congenital abnormality occasionally seen in adults.

Scimitar syndrome a very rare and variable congenital disorder characterized by an anomalous connection of the pulmonary vein with the IVC. The syndrome is mostly seen in very early infancy, but was now recognized in a 46-year-old woman, who was referred to the outpatient clinic of the department of cardiology with complaints of dizziness. Contrast enhanced computer tomography (CT) showed dextroposition of the heart and a large right pulmonary vein joined the inferior vena cava (IVC) just above the level of the diaphragm. The typical features of the syndrome are discussed.

Clinical symptoms of adult metachromatic leukodystrophy and arylsulfatase A pseudodeficiency.

OBJECTIVE: To determine the clinical symptoms in adult metachromatic leukodystrophy and in adult pseudodeficiency for arylsulfatase A. DESIGN: Case series. SETTING: University hospital. PATIENTS: Twenty-five adult patients with very low arylsulfatase A activity. RESULTS: In 13 patients, a diagnosis of adult metachromatic leukodystrophy was made. The main symptoms were dementia, behavioral abnormalities, ataxia, and polyneuropathy. In 12 patients, a diagnosis of arylsulfatase A pseudodeficiency was made. No characteristic clinical syndrome could be detected in these patients. CONCLUSIONS: Adult metachromatic leukodystrophy is a progressive metabolic disease with symptoms of demyelination of the central and peripheral nervous systems. Diagnosis must be confirmed by determination of arylsulfatase A activity and accumulation of sulfatides. Pseudodeficiency for arylsulfatase A can be confirmed or excluded by means of DNA analysis.

In vivo identification and quantitative evaluation of carrier-mediated transport of lactate at the cellular level in the striatum of conscious, freely moving rats.

Intracerebral dialysis has allowed the continuous, on-line measurement of lactate in the extracellular fluid (ECF) of conscious, freely moving rats. The rapid time response of the technique allows the direct determination of the time course of changes in lactate in ECF following externally imposed stimuli. The time course of lactate appearance in ECF was found to be considerably slower than that observed in tissue following electroconvulsive shock or during ischemia following cardiac arrest. The ECF data could be fit to an integrated Michaelis-Menten model that assumed reversible transport of lactate across the cell membrane. This transport was found to act only when energy supplies could maintain membrane integrity and function, since ECF levels of lactate failed to follow tissue levels after cardiac arrest when energy resources are depleted. The calculated rate of cellular lactate transport was two orders of magnitude faster than transport of lactate across the blood-brain barrier in the adult rat, and passive diffusion of lactate was not found to contribute significantly across either cell or blood-brain barriers. Probenecid, an inhibitor of acid transport, was able to block both the efflux of lactate from cell to ECF and the consequent reuptake of lactate by cells in the striatum of the rat following electroconvulsive shock or ischemia.

Measurement of acetylcholine release in freely moving rats by means of automated intracerebral dialysis.

The present study demonstrates the feasibility of measuring acetylcholine in perfusion samples collected by means of in vivo brain dialysis in the striata of freely moving rats. The output of the dialysis device was directly connected to an automated sample valve of a HPLC-assay system that comprises a cation exchanger, a post-column enzyme reactor, and an electrochemical detector. The presence of an acetylcholinesterase inhibitor (neostigmine) in the perfusion fluid was required for the detection of acetylcholine in the perfusate. Increasing concentrations of neostigmine induced increasing amounts of acetylcholine. Continuous perfusion with a fixed concentration (2 microM) of neostigmine resulted in gradually increasing amounts of collected acetylcholine over time although a considerable variation between successive samples exists. The brain dialysis technique was further validated by studying the effect of various drugs. Systemically administered atropine increased the output of acetylcholine, whereas the addition of tetrodotoxin to the perfusion fluid resulted in a complete disappearance of the neurotransmitter.

Results of treatment of center hemodialysis patients.

Four hundred eighty-three patients were maintained by hemodialysis in an outpatient hemodialysis center at the Mayo Clinic between 1963 and 1977. Although only 18 patients had experienced a myocardial infarction and 6 had had a cerebral infarction before beginning dialysis, 30 subsequently had acute myocardial infarction and 45 had a stroke. These two complications accounted for 48 of the 98 deaths that occurred during maintenance dialysis. Despite such complications, 183 patients were employed, 124 remained active at home or at school, and 115 were totally disabled. Survival of patients maintained solely by dialysis was 52% at 5 years. For the group as a whole, including patients who received their first allograft, the survival rate at 5 years was 65%.

The stone clinic effect in patients with idiopathic calcium urolithiasis.

The "stone clinic effect" refers to the effect of encouraging a high intake of fluid and avoiding dietary excesses on stone formation and growth in patients with urolithiasis. To determine the extent of this effect we reviewed the clinical courses of 108 patients with idiopathic calcium urolithiasis and indeterminant metabolic activity. There was no evidence of stone growth or new stone formation (metabolic inactivity) after a mean followup of 62.6 months in 63 of the 108 patients (58.3 per cent), including 12 of 17 (70.6 per cent) with hypercalciuria and 7 of 15 (46.7 per cent) with hyperuricosuria. Comparison of initial and followup 24-hour urine volumes demonstrated a significant increase in patients who were metabolically inactive at followup (p less than 0.0005), while no increase was detected in patients who were metabolically active at followup. We recommend that specific drug therapy should not be given to patients with idiopathic calcium urolithiasis until the stone clinic effect has been evaluated.

Subcellular fractionation of striatum: sedimentation properties of dopaminergic synaptosomes.

Linear sucrose density gradient centrifugation of a crude synaptosomal-mitochondrial preparation of rat striatum was performed at 82,500g for 7.5, 15 and 30 min and 1, 4 and 20 h. After centrifugation various marker enzyme activities were measured throughout the gradients, viz. tyrosine hydroxylase (TH) and DOPA decarboxylase (DD) as markers of dopaminergic synaptosomes, lactate dehydrogenase (LDH) as a general synaptosomal marker and monoamine oxidase (MAO) as a mitochondrial marker. At all centrifugation times the distribution patterns of TH and DD activity coincided almost perfectly. Notable differences were found between the sedimentation properties of these TH/DD-containing particles and LDH-containing particles: TH and DD were symmetrically distributed in the gradient much sooner than LDH, at all centrifugation times the top of the TH and DD curves was lying deeper in the gradient than the highest LDH activity, and TH and DD became enriched in the gradients to a much greater extent than LDH. It is concluded that rat striatal dopaminergic synaptosomes form a relatively homogeneous population of particles sedimenting faster into the gradients than the bulk of striatal synaptosomes does. This distinct sedimentation behaviour of the dopaminergic synaptosomes can be usefully applied for analytical purposes.

Localization of rat striatal monoamine oxidase activities towards dopamine, serotonin and kynuramine by gradient centrifugation and nigro-striatal lesions.

Subfractionation of the crude synaptosomal-mitochondrial fraction of rat striatum in a continuous sucrose gradient in a zonal rotor led to the following results. The distribution pattern of monoamine oxidase (MAO) activity towards dopamine (DA) was very similar to the pattern of MAO activity towards serotonin (5HT), but differed from the pattern of MAO activity towards kynuramine (KYN). As 5HT is specifically deaminated by MAO-A while KYN is a common MAO substrate, this supports earlier suggestions that in rat striatal preparations DA is deaminated preferentially by MAO-A. The patterns of the MAO activities towards DA and 5HT were clearly dissimilar, despite considerable overlap, to the patterns of tyrosine hydroxylase (TH) and DOPA decarboxylase (DD) activity, both marking the presence of striatal dopaminergic synaptosomes. The peak activities were separated and all patterns were symmetrical without showing a shoulder. This indicates that rat striatal MAO activity towards DA and 5HT is not specifically or for the greater part localized in dopaminergic terminals. We also investigated the effects of electrolytic and 6-hydroxydopamine lesions of the substantia nigra, both causing extensive degeneration of striatal dopaminergic terminals as appeared from the large decrease of striatal TH and DD activity. However, neither type of lesion induced a reduction of the MAO activity towards any of the substrates used. It is concluded that the amount of MAO activity towards DA and 5HT (probably MAO-A activity) present in dopaminergic terminals is very low compared with the total activity of this enzyme in rat striatal tissue.

Renal tubular acidosis. A new look at treatment of musculoskeletal and renal disease.

The clinical and laboratory manifestations, roentgenographic findings, and treatment of 48 patients with renal tubular acidosis who were examined at the Mayo Clinic during a 10-year period were reviewed. The initial clinical presentations of the 48 patients in the series included rheumatic complaints in 25 and recurrent nephrolithiasis in 23. Of the 23 patients who presented with nephrolithiasis, 8 also had musculoskeletal symptoms. Thirty-three of the 48 patients had careful follow-up of a total of 68 musculoskeletal complaints. Forty of these symptoms (59%) diminished after treatment of the renal tubular acidosis with orally administered alkali. Associated connective tissue diseases were present in 12 patients. Thirty-four patients had roentgenographic evidence of renal calculi. Of this group, 19 were followed up with sequential roentgenographic studies of the kidneys for more than 1 year during therapy. Of 15 patients treated orally with alkali, 13 had metabolically inactive renal stone disease. Three of the patients treated orally with phosphorus supplements had persistent metabolically active renal stone disease. Patients with renal tubular acidosis often present with musculoskeletal manifestations and renal lithiasis, both of which frequently subside with the treatment of the renal tubular acidosis.

Treatment of renal lithiasis associated with renal tubular acidosis.

In order to determine the incidence of renal lithiasis in patients with renal tubular acidosis and the effect of therapy on further stone formation, we reviewed the clinical and laboratory manifestations, X-ray findings, and treatment of 48 patients with renal tubular acidosis who were seen at the Mayo Clinic during the years 1970-1980. Thirty-four patients (70%) had radiological evidence of renal lithiasis which was the presenting symptom in 23 (48%) patients. In every instance the calculi were multiple and, with one exception, bilateral. While receiving therapy, 19 patients with renal lithiasis were followed for longer than one year with sequential uroradiographic studies. Fifteen of these patients were treated with oral base alone and thirteen had no evidence of new stone formation or continued growth of existing stones during therapy. The two patients with X-ray evidence of continued stone formation admitted to poor compliance. Four patients received initial treatment with an oral phosphorus supplement. Three of these four patients had radiographic evidence of continued renal stone formation during three, five and eight years of phosphate therapy. We conclude renal lithiasis is a frequent complication of renal tubular acidosis, and adequate base replacement is effective therapy to stop continued stone formation while oral phosphate therapy alone is often ineffective.

Idiopathic hypercalciuria: hydrochlorothiazide decrease urinary calcium without altered renal response to parathyroid hormone.

Hydrochlorothiazide (HTZ) therapy reduces the urinary excretion of calcium (UCa V) in patients with idiopathic hypercalciuria (IH). To test the role of parathyroid hormone (PTH), namely the possibility that HTZ sensitizes the kidney to PTH as the sole or contributory cause of decreased UCa V associated with HTZ therapy, we measured urinary excretion of calcium (UCa V) and cAMP (UcAMP V), the tubular reabsorption of phosphate (TRP), plasma immunoreactive PTH, and the renal response to infused PTH (change in UcAMP V and TRP) in 10 patients with IH. Patients were studied before (control) and after 4 weeks of treatment with HTZ (100 mg/day). HTZ therapy significantly reduced UCa V (mean change, -122 +/- 19 mg/24 h). The UcAMP V, TRP, and plasma levels of calcium, phosphorus, and immunoreactive PTH were initially within the normal range and did not change significantly during HTZ therapy. PTH infusion resulted in a significant increase in the UcAMP V and a significant decrease in TRP during both control and HTZ therapy studies. There was, however, no significant difference in the degree of these renal responses to PTH infusion during the control vs. HTZ therapy studies. We conclude that the hypocalciuric effect of HTZ in patients with IH is independent of changes in PTH secretion, and that HTZ does not cause general sensitization of the nephron, namely proximal tubules, to PTH, as assessed by an increase in UcAMP V and a decrease in TRP.

Reversible nonoliguric acute renal failure associated with zomepirac therapy.

Zomepirac sodium (Zomax) is a nonsteroidal anti-inflammatory agent with analgesic properties which was recently released for clinical use in this country. We report here a case of nonoliguric acute renal failure associated with zomepirac sodium therapy. This acute renal failure improved upon cessation of zomepirac treatment. Renal biopsy disclosed the presence of a tubulointerstitial nephritis, which was thought to have been responsible for the acute renal failure in this patient. Clinicians should be aware of the potential nephrotoxicity of zomepirac sodium and use caution in its administration, especially in patients with compromised intravascular volume status, hypertension, or preexistent chronic renal disease.

Two patients with an unusual form of type II fucosidosis.

Two brothers with an unusual form of fucosidosis are presented, providing further evidence for the clinical heterogeneity of the disease. The patients have several characteristics of type II, but from the point of view of progression rate and survival, they resemble more type III. However, the characteristic skin lesions of type III are not seen. In contrast to all other subtypes, a dry, thin skin is observed. The authors tend to classify these patients as a "slow motion" type II variant. Both in leukocyte lysates and plasma, severe alpha-L-fucosidase deficiency was established. In the parents, intermediate alpha-L-fucosidase activities were observed in leukocytes, but normal values in plasma, indicating that plasma is not suitable for carrier detection in this family. It is felt that no conclusions regarding clinical subtypes of fucosidosis can be drawn without careful characterization of the mutant enzyme in the primarily affected tissues.

Orthophosphate therapy decreases urinary calcium excretion and serum 1,25-dihydroxyvitamin D concentrations in idiopathic hypercalciuria.

Orthophosphate treatment of patients with idiopathic hypercalciuria reduces the urinary excretion of calcium. To examine the role of altered vitamin D metabolism in reducing the renal excretion of calcium, we studied 11 patients with idiopathic hypercalciuria before and after 2 weeks of treatment with oral neutral orthophosphate (2 g phosphorus/day). Variables measured were urine calcium and phosphorus and seseserum calcium, phosphorus, immunoreactive parathyroid hormone, and 1,25-dihydroxyvitamin D [1,25-(OH)2D]. Oral phosphate treatment significantly decreased urine calcium excretion [mean change (delta), -123 mg/24 h], increased urine phosphorus (mean delta, serum levels of 1,25-(OH)2D (mean delta, -22 pg/ml). Pretreatment levels of 1,25-(OH)2D were high when compared with levels in age-matched controls, whether assessed as the arithmetic mean (57 vs. 33 pg/ml; P < 0.025), the logarithmically normalized (42 vs. 27 pg/ml). Phosphate treatment decreased serum levels of 1,25-(OH)2D to a mean of 35 pg/ml (logarithmically normalized mean, 22 pg/ml; median, 21 pg/ml), values not significantly different from those of normal controls. Serum calcium and phosphorus concentrations were not changed by treatment. Serum immunoreactive parathyroid hormone values increased minimally within the normal range (mean delta, +2 microleq/ml; P <0.025). We conclude that the effect of oral phosphate therapy in decreasing urinary calcium excretion may involve the reduced synthesis of 1,25-(OH)2D, independent of altered parathyroid function.

Glutamine therapy of cystinuria.

We studied the urinary excretion of cystine, acids, and cystine crystalluria in five patients with homozygous cystinuraia before and during oral glutamine therapy. Oral glutamine did not change the absolute urinary excretion or fractional excretion of cystine in our patients and did not significantly affect urinary pH. Cystine crystalluria was present before and during oral glutamine therapy.