Controlled study of haloperidol, pimozide and placebo for the treatment of Gilles de la Tourette's syndrome

The results of this controlled study of the treatment of 57 patients with Gilles de la Tourette's syndrome suggested that both haloperidol and pimozide were more effective than placebo, but that haloperidol was slightly more effective than pimozide. Adverse effects occurred more frequently with haloperidol vs placebo than with pimozide vs placebo, but the frequency was not significantly different for haloperidol compared with pimozide. Clinically significant cardiac effects did not occur at a maximum dosage of 0.3 mg/kg or 20 mg/d for pimozide and 10 mg/d for haloperidol. However, the QTc interval was prolonged during pimozide treatment compared with that during haloperidol treatment, although the values for both medications were not in an abnormal range.     

Case report: extensive brain calcification in hypoparathyroidism.

It is well known that most patients with hypoparathyroidism have radiologically detectable basal ganglia calcification. Not as well known is that the brain calcinosis may be more extensive. We describe a 55-year-old woman with a 44-year history of symptomatic idiopathic hypoparathyroidism who has extensive calcification of her cerebrum and cerebellum as well as her basal ganglia, evident on computed tomography of the head. When first evaluated here 32 years ago, plain radiography of the skull demonstrated calcification of both caudate and lentiform nuclei (basal ganglia). Despite fair control of her serum calcium level, she has developed focal seizures, possibly related to the calcinosis of her brain.     

A new tool for consultation-liaison funding: modified DRGs to reflect psychiatric comorbidity.

Funding for consultation-liaison (C-L) psychiatry remains an overriding obstacle to its implementation and practice. Several methods have been described to access funds for this subspecialty of psychiatry, but none has been enacted as a policy by third party payers to reimburse adequately for the service. In addition, although the consultation portion of the effort can be reimbursed in part in some cases through fee for services, the liaison portion is dependent on the donation of psychiatry time or the largesse of the host department. The efforts at Stanford to capitalize on the findings that psychiatric and medical comorbidity results in prolonged length of hospital stay and increased health resource utilization suggest that specific DRGs would be important patient groups to screen and charge for psychiatric services. Furthermore, DRGs that are accompanied by a high frequency of psychiatric comorbidity are a "target" for an additional funding aliquot to assess and manage the patient's psychiatric status.     

The origins of life -- the 'protein interaction world' hypothesis: protein interactions were the first form of self-reproducing life and nucleic acids evolved later as memory molecules

The 'protein interaction world' (PIW) hypothesis of the origins of life assumes that life emerged as a self-reproducing and expanding system of protein interactions. In mainstream molecular biology, 'replication' refers to the material copying of molecules such as nucleic acids. However, PIW is conceptualized as an abstract communication system constituted by the interactions between proteins, in which 'replication' happens at the level of self-reproduction of these interactions between proteins. Densely concentrated peptide interaction systems may have reproduced and expanded as 'protocell' vesicles surrounded by lipid bi-layer membranes. Protocells led to the emergence of proto-RNA molecules of greater chemical stability which served as chemically differentiated 'memories' of peptide interaction states, thereby facilitating the reproduction and expansion of protocells. Simplification-driven expansion led to the selection of biotic amino acids and the reduction of the typical RNA alphabet to the four usual bases (A, C, G and U). Dense interactions between RNA molecules led to the emergence of the RNA interaction subsystem of the cell, and to the emergence of 'memories' of RNA interactions in the form of DNA molecules with greater chemical stability. The expansion of DNA molecule interactions led to the dense clustering and encapsulation of DNA molecules within the cell nucleus. RNA molecules therefore serve as memories of protein interactions and DNA molecules are memories of RNA interactions. We believe that the PIW hypothesis is more evolutionarily plausible than the mainstream RNA world hypothesis, and has greater explanatory power.     

Association analysis of 5-HTTLPR variants, 5-HT2a receptor gene 102T/C polymorphism and migraine

It is well known that migraine has a strong genetic component, although the type and number of genes involved is not yet clear. There is evidence to suggest that serotonin-related genes participate in the pathogenesis of migraine. Previous studies have shown that gender differences influence the serotonergic neurotransmission and, in addition, the migraine prevalence is higher in females than males. Therefore, we investigated the functional polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) and the 102T/C polymorphism of the 5-HT2A receptor gene in the Hungarian female population. These genes were analysed in 126 migraine sufferers (with or without aura)and 101 unrelated healthy controls using case control design. A borderline association (chi2 = 3.84, df = 1, p = 0.049; OR = 1.45, 95% CI = 1.00-2.12) between 5-HTTLPR short (S) allele and migraine was found. No significant difference between migraine sufferers and controls was observed for the 102T/C polymorphism of 5-HT2A receptor gene. Furthermore, there was no significant interaction between5-HTTLPR and 102T/C polymorphisms in our study population. In conclusion, our results support that the genetic susceptibility of migraine may be associated with a locus at or near the 5-HT transporter gene.     

Sucrose sham feeding decreases accumbens norepinephrine in the rat

Noradrenergic projections from the dorsomedial medulla reach the shell of the nucleus accumbens (NAcc), a structure implicated in both reward and feeding behavior. Despite this relationship, the effect of food reward on accumbens norepinephrine (NE) remains uninvestigated. In the course of assessing dopamine (DA) in the NAcc during sucrose ingestion [0.03, 0.1, and 0.3 M; Am. J. Physiol., Regul. Integr. Comp. Physiol., 286 (2004) R31], we also analyzed NE in the microdialysis samples from 14 ad-libitum-fed male rats. In contrast to DA, which increased with sucrose concentration (+20-47%) during sham feeding, in the same animals, NE levels were reduced (approximately -20%), regardless of sucrose concentration. These results demonstrate a novel relationship between accumbens DA and NE during orosensory stimulation with a preferred nutrient.     

Effect of vinpocetine on retrograde axoplasmic transport

Vinpocetine, a derivate of vincamine, is widely used in the clinical pharmacotherapy of cerebral circulatory diseases. Herewith we report on a novel effect of vinpocetine: inhibition of retrograde axoplasmic transport of nerve growth factor (NGF) in the peripheral nerve. Blockade of retrograde transport of NGF results in transganglionic degenerative atrophy (TDA) in the segmentally related ipsilateral superficial spinal dorsal horn, which is characterized by depletion of the marker enzymes fluoride-resistant acid phosphatase (FRAP) and thiamine monophosphatase (TMP). At the same time, pain-related neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP), are depleted from lamina I-III from the segmentally related, ipsitateral Rolando substance of the spinal cord. On the basis of these experiments it is suggested that vinpocetine may result in a locally restricted decrease of nociception, that might be useful in clinical treatment of intractable pain. Pilot self-experiments support this assumption.     

The effect of trimodal prehabilitation on the physical and psychological health of patients undergoing colorectal surgery: a randomised clinical trial

Prehabilitation aims to increase the endurance capacity of patients who are awaiting major surgery. However, there are no studies investigating the implementation of this demanding and expensive intervention in low-income countries. This study aimed to assess the impact of a 4-week trimodal prehabilitation program on the physical and psychological health of patients waiting for colorectal surgery compared with a control group managed according to enhanced recovery after surgery principles supplemented by nutritional care. This study was a single-centre, randomised controlled trial. The primary outcome measures for the physical aspects were 6-minute walking distance (6MWD) and incentive spirometry, whereas the psychological elements were measured using the 36-item short form survey questionnaire and the hospital anxiety and depression score. In total, data from 149 patients were analysed (77 in the prehabilitation group and 72 in the control group). At the time of surgery, patients in the prehabilitation group had improved 6MWD and incentive spirometry compared with the control group (median (IQR [range]) percentage improvement 131% (112–173 [68–376]) vs. 107% (99–120 [63–163]); p < 0.001 and 113% (100–125 [75–200]) vs. 100% (100–112 [86–167]); p < 0.001 respectively). Patients in the prehabilitation group also had reduced anxiety scores compared with the control group (mean (SD) anxiety score (4 (3) vs. 5 (3) respectively; p = 0.032). However, these effects did not translate into improvements in postoperative mortality and morbidity, or a reduction in duration of hospital stay. Trimodal (physical, emotional and nutritional) prehabilitation is able to improve functional status as well as some parameters of emotional and physical well-being of patients waiting for colorectal surgery.