Cranioplasty: A Multidisciplinary Approach.

Decompressive craniectomy (DC) is an operation where a large section of the skull is removed to accommodate brain swelling. Patients who survive will usually require subsequent reconstruction of the skull using either their own bone or an artificial prosthesis, known as cranioplasty. Cranioplasty restores skull integrity but can also improve neurological function. Standard care following DC consists of the performance of cranioplasty several months later as historically, there was a concern that earlier cranioplasty may increase the risk of infection. However, recent systematic reviews have challenged this and have demonstrated that an early cranioplasty (within three months after DC) may enhance neurological recovery. However, patients are often transferred to a rehabilitation unit following their acute index admission and before their cranioplasty. A better understanding of the pathophysiological effects of cranioplasty and the relationship of timing and complications would enable more focused patient tailored rehabilitation programs, thus maximizing the benefit following cranioplasty. This may maximise recovery potential, possibly resulting in improved functional and cognitive gains, enhancement of quality of life and potentially reducing longer-term care needs. This narrative review aims to update multi-disciplinary team regarding cranioplasty, including its history, pathophysiological consequences on recovery, complications, and important clinical considerations both in the acute and rehabilitation settings.

Modulation of the absorption coefficient at 1.3 µm in Ge/SiGe multiple quantum well heterostructures on silicon.

We report modulation of the absorption coefficient at 1.3 µm in Ge/SiGe multiple quantum well heterostructures on silicon via the quantum-confined Stark effect. Strain engineering was exploited to increase the direct optical bandgap in the Ge quantum wells. We grew 9 nm-thick Ge quantum wells on a relaxed Si0.22Ge0.78 buffer and a contrast in the absorption coefficient of a factor of greater than 3.2 was achieved in the spectral range 1290-1315 nm.

Reduced narcotic and sedative utilization in a NICU after implementation of pain management guidelines.

OBJECTIVE: To assess the opioid and benzodiazepine usage in a level IV NICU after implementation of pain guidelines. STUDY DESIGN: Guidelines were developed for infants undergoing surgical procedures and infants on mechanical ventilation. Data collected for period 1 (July to December 2013) and period 2 (March to August 2014). RESULTS: Gestational age, birth weight and infants with hypoxic respiratory failure or requiring major procedures were comparable in two periods. Number of patients exposed to opioids decreased from 62.9% (129/205) in period 1 to 32.8% (82/250) in period 2, P=<0.001. Cumulative dose exposure decreased, opioids in morphine equivalent dose, mg kg-1 (1.64 (0.38 to 6.94) vs 0.51 (0.04 to 2.33), P=0.002), sedatives in midazolam equivalent, mg kg-1 (0.16 (0.03 to 7.39) vs 0.10 (0.00 to 4.00), P=0.03). Ten patients required treatment for iatrogenic opioid withdrawal versus only three in post guideline, P=0.02. CONCLUSIONS: Evidence-based guidelines led to significant reduction in opioids and sedatives exposure, and in the number of infants requiring methadone for iatrogenic narcotic dependence.

Cortical modulation of the cardiovascular system.

Cortical modulation of central cardiovascular control mechanisms has been recognized for many decades. However, it is only recently that the mechanisms underlying cortical influences on circulatory function have been systematically examined. This review considers the view that certain regions of the cerebral cortex, including the medial prefrontal cortex (MPFC) and insular cortex (IC), participate in specific aspects of central circulatory control. Anatomical investigations indicate that these cortical areas are connected with hypothalamic, midbrain, pontine and medullary brain regions involved in cardiovascular control. Lesions of the MPFC and IC have demonstrated modulation of the activity of cardiovascular reflexes such as the baroreceptor heart rate reflex and involvement in conditioned cardiovascular responses. Electrophysiological studies have provided evidence that cortical regions are able to influence premotor sympathoexcitatory vasomotor neurons within the rostral ventrolateral medulla and subsequently alter sympathetic vasomotor tone. Cortical regions such as the IC receive visceral sensory information arising from baroreceptors and chemoreceptors within the cardiovascular system. In contrast, the MPFC receives afferents predominantly from limbic sources, although its outputs include structures associated with central sympathetic vasomotor control. Cortical modulation of circulatory function has been demonstrated in man and may underlie the cardiovascular components of a number of conditions. It is suggested that cortical areas involved in visceral sensory or visceral motor processes associated with circulatory function may be involved in generation of patterns of cardiovascular responses specific for certain behaviours.

Modulation of retinoic acid-induced differentiation of human leukemia (HL-60) cells by serum factors and sphinganine.

The human cell line HL-60 was used to investigate the role of protein kinase C in the regulation of retinoic acid-induced maturation of promyelocytic leukemia cells by growth and differentiation factors found in serum. Cells grown in serum-containing medium differentiated less than cells in serum-free medium due to several factors, including albumin binding of retinoic acid. Addition of an inhibitor (sphinganine) of protein kinase C, an enzyme that participates in cellular responses to many serum factors, facilitated the retinoic acid-induced differentiation. Cells treated with both retinoic acid and sphinganine produced more superoxide when stimulated by formylmethionylleucylphenylalanine; hence, this combination generated a more functional population of cells. The ability of sphinganine to promote retinoic acid-induced differentiation suggests that retinoic acid therapy might be improved by the concurrent use of a modulator of protein kinase C activity.

Differential effects of long-chain (sphingoid) bases on the monocytic differentiation of human leukemia (HL-60) cells induced by phorbol esters, 1 alpha, 25-dihydroxyvitamin D3, or ganglioside GM3.

Conditions were developed to prolong the ability of sphinganine, a potent inhibitor of protein kinase C, to block the phorbol ester-induced adherence of HL-60 cells beyond 24 h. The loss of inhibition after this time seen previously (A.H. Merrill, Jr., A.M. Sereni, V.L. Stevens, Y.A. Hannun, R.M. Bell, and J.M. Kinkade, Jr., J. Biol. Chem., 261: 12610-12615, 1986), which appeared to be due to metabolism of this long-chain base, was overcome by supplying sphinganine daily. After 4 days, phorbol myristate acetate-induced adherence was inhibited approximately 50% by sphinganine. Sphinganine significantly decreased the expression of nonspecific esterase induced by phorbol myristate acetate in the nonadherent cells, indicating that other aspects of maturation besides adherence were blocked. The effects of daily sphinganine treatments on the monocytic differentiation induced by 1 alpha-25-dihydroxyvitamin D3 or ganglioside GM3 were also investigated. The increases in nonspecific esterase expression, nitroblue tetrazolium reduction, and morphological maturation caused by either agent were unaffected by the long-chain base. In addition, the changes in several cell surface antigens caused by 1 alpha,25-dihydroxyvitamin D3 were unaltered by sphinganine. Although phorbol esters, 1 alpha,25-dihydroxyvitamin D3, and ganglioside GM3 all induce the maturation of HL-60 cells along the monocytic lineage, the finding that sphinganine only affected the differentiation initiated by phorbol esters, in which protein kinase C clearly is a major regulator, suggests that this enzyme does not play a major role in these other pathways of differentiation.

Hypertonic cryohemolysis and the cytoskeletal system.

Hypertonic cryohemolysis is defined as the lysis of erythrocytes in a hypertonic environment when the temperature is lowered from above 15-18 degrees C below that temperature. This has been found to be a general phenomenon (that is, whether the solute is charged or not), to exhibit interesting temperature characteristics and to be preventable by agents such as valinomycin which tend to dissipate the concentration gradient across the cell membrane. As yet, no clear information is available to translate this phenomenon to the molecular level and to relate it to current structure/function concepts in the erythrocyte membrane. In this study, data are presented which would indicate on the basis of two entirely separate methodologies that the spectrin-actin cytoskeletal framework is involved in this phenomenon. The first of these methodologies is based on radiation-induced ablation of cryohemolysis and indicates that an intact macromolecular complex of an order of 16000 000 daltons is required for cryohemolysis with hypertonic NaCl. The second methodology is based on selective cross-linking of spectrin and actin in the agent diamide, which resulted in concentration-dependent suppression of cryohemolysis. Polyacrylamide gel electrophoresis of the erythrocyte from diamide-treated cells showed intense protein aggregation with loss of spectrin-actin and bands 4.1, 4.2. We conclude that the spectrin-actin cytoskeletal system possibly including its interaction with phospholipids is the key to the phenomenon of hypertonic cryohemolysis.

Right atrial stretch activates neurons in autonomic brain regions that project to the rostral ventrolateral medulla in the rat.

Activation of the cardiac mechanoreceptors results in changes in sympathetic nerve activity and plays an important role in the responses elicited by elevated blood volume. Stimulation of the reflex influences several key autonomic regions, namely the paraventricular nucleus (PVN), the nucleus of the tractus solitarius (NTS) and the caudal ventrolateral medulla (CVLM). Neurons in these regions project directly to the rostral ventrolateral medulla (RVLM), a critical region in the generation of sympathetic vasomotor tone. The aim of the present experiments was to determine whether neurons in the PVN, NTS and CVLM that are activated by cardiac mechanoreceptor stimulation also project to the RVLM. Animals were prepared, under general anesthesia, by microinjection of a retrogradely transported tracer into the pressor region of the RVLM, and the placement of a balloon-tipped cannula at the junction of the right atrium and the superior vena cava. On the experimental day, in conscious rats, the balloon was inflated to stimulate cardiac mechanoreceptors (n = 9), or left uninflated (control, n = 8). Compared with controls, there was a significantly increased number of Fos-immunoreactive neurons (a marker of activation) in both the PVN (2.5-fold) and NTS (two-fold), but this was not seen in the CVLM. Compared with controls, a significant number of the neurons in the PVN (8%) and NTS (4.0%) that projected to the RVLM were activated. The data suggest that subgroups of RVLM-projecting neurons located in the PVN and NTS are involved in the central reflex pathway activated by cardiac mechanoreceptor stimulation.

Prophylaxis of oral candidiasis with clotrimazole troches.

Oropharyngeal candidiasis is frequently a complication of patients with altered immune states. Clotrimazole troches are effective in the treatment of Candida and were evaluated in this study in a prophylaxis regimen. Patients with malignant neoplasms who were receiving chemotherapy and renal transplant recipients who were receiving immunosuppressives were randomized to receive either clotrimazole (10 mg) or placebo troches three times a day in a prospective, double-blinded study. Eighty-four patients were randomized into the study, 18 patients with leukemia, 19 patients with malignant neoplasms, and 47 patients with renal transplants. Among all patients, thrush developed in 57% while receiving placebo compared with 13% while receiving clotrimazole prophylaxis. Prophylaxis showed significant benefit for the renal transplant recipients and for patients with solid malignant neoplasms, but not for the leukemic patients. Clotrimazole troches are effective in preventing oral candidiasis in a select group of patients.

Molecular size of the Rh0(D) antigen of the human erythrocyte in situ by radiation inactivation.

Radiation inactivation was used to determine the molecular size of the RhO(D) antigen of isolated membranes and of the intact human erythrocyte. Isolated membranes were frozen and irradiated at -50 degrees C. After thawing, the bound 14C-anti-D was measured and the log residual Rh(D) antigen activity was plotted against the radiation dose. A mol. wt of 60,000 was calculated. Intact human erythrocytes frozen in the presence of cryoprotective reagents were also studied. Rh(D) antigen inactivation occurred as a single exponential function of radiation dose which also yielded a mol. wt of approx. 56,000 upon analysis by classical target theory.

Treatment and prevention of oropharyngeal candidiasis.

As more potent antibacterial drugs are used to combat infections and as more patients with impaired defenses against infection are treated, other organisms, like fungi, have become important pathogens. Fungi of all types may appear in this setting, but Candida species are the most common, usually beginning as an infection in the oropharynx. Although oropharyngeal candidiasis usually remains localized, it may spread elsewhere, leading to a fatal outcome. Controversy still exists regarding the best drug to prevent or treat oropharyngeal candidiasis, but clotrimazole given as a troche may be the best choice at the moment owing to its high clinical success rate, safety, cost effectiveness, and high patient acceptability. There remains a need for more randomized and controlled studies comparing the efficacy of nystatin, ketoconazole, and clotrimazole in high-risk patients in whom invasive candidiasis remains a frequent problem.

Medial prefrontal cortex depressor response: role of the solitary tract nucleus in the rat.

The depressor response elicited by unilateral low intensity electrical stimulation of the rat ventral medial prefrontal cortex may be mediated by a connection with the solitary tract nucleus. We tested this hypothesis by (i) examining the influence of medial prefrontal cortex stimulation on the induction of Fos-like immunoreactivity in neurons in the medulla oblongata, and (ii) by testing the effect of inhibition of solitary tract nucleus neurons on the medial prefrontal cortex stimulation-evoked depressor response. Depressor responses (>10 mmHg) were elicited by electrical stimulation of the medial prefrontal cortex every minute for 1 h ('Stimulated' group). Control animals were treated identically but did not receive electrical stimulation ('Unstimulated' group). Neurons exhibiting Fos-like immunoreactivity were abundant at the stimulation site which included the infralimbic area, and dorsal peduncular cortex. Medullary Fos-like immunoreactivity observed in the 'Stimulated' and 'Unstimulated' groups exceeded levels observed in untreated rats and was detected in the rostral, caudal and intermediate areas of the ventrolateral medulla, and the commissural, intermediate, medial and lateral regions of the solitary tract nucleus, as well as the medial vestibular nucleus, and the dorsal motor nucleus of the vagus. The number of neurons displaying Fos-like immunoreactivity in the ipsilateral solitary tract nucleus and caudal ventrolateral medulla of the 'Stimulated' group was found to be significantly elevated compared to the contralateral side (P<0.05), and the 'Unstimulated' group bilaterally. Inhibition of solitary tract nucleus neurons using bilateral injections of the GABA(A) receptor agonist muscimol (44 pmol/25 nl) inhibited the sympathetic vasomotor baroreflex and attenuated the depressor and sympathoinhibitory response to medial prefrontal cortex stimulation by 62% and 65%, respectively. These findings suggest that the projection from the medial prefrontal cortex to the solitary tract nucleus is excitatory and support the hypothesis that the depressor response elicited by medial prefrontal cortex stimulation is mediated, in part, by a cortico-solitary projection which activates the intramedullary baroreflex pathway.

Mosaicism for a chromosome 8-derived minute marker chromosome in a patient with manifestations of trisomy 8 mosaicism.

We describe a patient with manifestations of the mosaic trisomy 8 syndrome and mosaicism for a minute marker chromosome. Fluorescence in situ hybridization (FISH) with a chromosome 8 probe confirmed that the marker was derived from chromosome 8. This is the smallest piece of chromosome 8 to be reported in a patient with mosaic trisomy 8 syndrome. When the clinical picture is strongly suggestive of trisomy for a specific chromosome region, we believe that FISH can be used to test markers in a guided, rather than random, fashion.

Boy with bilateral retinoblastoma due to an unusual ring chromosome 13 with activation of a latent centromere.

We present a patient with bilateral retinoblastoma and developmental delay who has an abnormal male karyotype containing 47 chromosomes, including an acentric derivative chromosome 13. We postulate that the derivative 13 occurred after a break at 13q14, with the proximal portion of the chromosome forming a ring and the distal portion undergoing duplication. Thus, this patient is trisomic for 13q14-->qter. The derivative chromosome with duplicated distal portion (13q14-->qter) lacked the 13 centromere and was negative for chromosome 13 alpha-satellite DNA by low stringency FISH. Nevertheless, this chromosome is stably transmitted in lymphocytes and fibroblasts. A single primary constriction was observed at band 13q21, consistent with activation of a latent centromere (neocentromere) at this band. The neocentromere on der(13) was positive for multiple centromeric proteins, suggesting that it acts as the functional centromere. By FISH, the Rb gene was present on the normal 13, the proximally derived ring chromosome, but not on the derivative chromosome. Although there was no evidence for disruption of the Rb gene, this chromosome rearrangement most likely results in abnormal expression of the Rb gene product.

Pharmacologic treatment of hypersexuality and paraphilias in nursing home residents.

PURPOSE: To discuss the pharmacologic options for treatment of hypersexuality or paraphilias in nursing home residents. DATA SOURCES: A MEDLINE search was conducted for English-language articles published over the past 20 years and was supplemented by a search of bibliographies of relevant articles. STUDY SELECTION: Case reports of pharmacologic treatment of hypersexual or paraphilic behavior were selected only if the patient receiving treatment was an older person and/or cognitively impaired. DATA EXTRACTION: Case reports were grouped according to the class of the pharmacologic agent used (antiandrogens, estrogens, GnRH analogues, or serotonergic drugs). Each case report was evaluated for pharmacologic agent administered, route of administration, duration of therapy, therapeutic response, and incidence of side effects. CONCLUSIONS: Nursing home residents who display hypersexual or paraphilic behavior are extremely difficult to manage. Before initiating pharmacotherapy to control unwanted sexual behaviors, the current drug regimen should be evaluated carefully for drugs that may be causing or exacerbating the behavior. Case reports suggest that antiandrogens, estrogens, GnRH analogues, and serotonergic medications may be useful when other methods have failed. Controlled comparative trials of these agents are needed to establish their efficacy clearly.

The Senior Care Study. The optimal use of medications in acutely ill older patients.

UNLABELLED: Geriatric assessment units have improved pharmacotherapy for their patients by decreasing the number of medications prescribed. The Senior Care Study, a randomized controlled trial, compared a multidisciplinary-team approach to patient care to the standard medical practice of the institution. As a part of the trial, the effectiveness of an interdisciplinary team intervention in improving the use of medications was studied. Study goals were to decrease medications used, decrease unnecessary medications, and improve medication choices in our acutely ill inpatient population. A pharmacist interviewed all experimental patients and patient records, and presented medication concerns and recommendations at a team conference. MEDICATIONs were counted on admission and on the third day, sixth week, and third month after randomization. MEDICATIONs were paired with patient problems. MEDICATION: problem pairs were judged as inappropriate choices if there were potential side effects that would affect patient function, and if better alternatives were available. The 215 control and 221 experimental patients in the study were similar in age, sex, place of origin, and number of medications on admission. Experimental patients took fewer medications than controls on the third day (5.3 versus 5.9, P less than .05). Experimental patients received fewer multiple unpaired medications (11% versus 19%, P less than .025) and fewer inappropriate medication choices (20% versus 37%, P less than .005). The results suggest that the team intervention was effective in improving pharmacotherapy in the acute-care setting.

The Senior Care Study. A controlled trial of a consultative/unit-based geriatric assessment program in acute care.

Successful models of inpatient geriatric assessment have often involved long hospital stays, specialized interdisciplinary care, and prolonged follow-up, which are difficult to achieve within a prospective payment system. A randomized clinical trial was undertaken to evaluate the efficacy (maintenance or improvement in mental, emotional, and physical function) of using a geriatric assessment process in acute hospital care without increasing hospital charges or lengths of stay. Four hundred thirty-six patients greater than or equal to 75 years of age were randomly allocated to treatment (n = 221) or control (n = 215) conditions. Patients in the treatment group were admitted to a special unit and evaluated on admission by an interdisciplinary team, which developed a care plan. Although primary care was provided by the patient's own physician, the team followed the patients as consultants on the unit in the hospital, and by telephone for 2 months after discharge. The control group was placed on other units and received usual hospital care. The treatment and control groups were similar at study entry. At follow-up, there were no significant differences between the groups with respect to lengths of stay, hospital charges, mortality, change in physical function, or change in mental function. The treatment group changed more often in measured emotional function (chi 2 = 6.213, P = .045). This study indicates that it is feasible to implement consultative interdisciplinary team care in the acute-care hospital, but that its efficacy may be limited when applied to an unselected group of older patients.

Regional haemodynamic responses to activation of the medial prefrontal cortex depressor region.

Electrical or chemical stimulation of the medial prefrontal cortex (MPFC) produces depressor and sympathoinhibitory responses. To characterise the MPFC depressor response more fully, we determined the regional haemodynamic changes which occurred in response to stimulation of the MPFC. In halothane-anaesthetised rats, we recorded arterial blood pressure and renal, superior mesenteric, and iliac arterial vascular conductance using miniaturised Doppler flow probes. Electrical stimulation of the MPFC (50-100 microA) was used to map the location of the depressor region. Increases in vascular conductance (or increases in blood flow) were recorded from the renal (+2.3+/-0.5 kHz/mmHgx10(3)), mesenteric (+4.4+/-0.4 kHz/mmHgx10(3)), and iliac (+8.3+/-1.0 kHz/mmHgx10(3)) vascular beds in response to stimulation of the MPFC depressor region coinciding with the ventral infralimbic (IL) and dorsal peduncular (DP) cortical areas. Similar responses were obtained after microinjection of the chemical excitant L-glutamate (n=3, 100 nl, 100 mM), indicating that the responses were due to excitation of cell bodies and not due to axons traversing the area. Administration of the nitric oxide synthesis inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 25 micromol/kg, i.v., n=5) significantly reduced the MPFC depressor response (51%, 12.5+/-1.2 to 6.1+/-2.5 mmHg). The increases in conductance in the hindquarter and mesenteric vascular beds were significantly reduced after L-NAME treatment (mesenteric by 77%, iliac by 70%), but there was no significant reduction of renal flow (35%). These observations indicate that the depressor region of the MPFC is localised to ventral regions (IL and DP) and that the depressor response is mediated by increased conductance in the hindquarters and mesenteric vascular beds. Furthermore, the depressor response may be mediated, in part, by release of nitric oxide in these vascular beds.

A simple and reliable method for construction of parallel multibarrel microelectrodes.

A modification to the method of construction of parallel or "piggy-back" electrodes for extracellular single-unit recording combined with iontophoresis is described that facilitates the alignment of the two components of the array. The method involves the use of an orthogonal viewing device (a pair of mirrors mounted symmetrically at 45 degrees to the horizontal), which produces a pair of virtual images of the electrode components that can be viewed with a microscope. A slight displacement between the electrodes is easily detected as an uneven separation between the electrode images. The positions of the electrode components are adjusted until there is no visible separation of the electrodes or their virtual images.

Is there a fountain of youth? A review of current life extension strategies.

Life expectancy has dramatically increased in industrialized countries since the 1900s due to advances in disease prevention and treatment, and improvements in nutrition and infant mortality. Thus, as a society we are living longer and experiencing more of the changes and declines associated with aging. Although the factors that cause our bodies to age are unknown, various medical interventions have been proposed and explored to prevent the process. Published research on aging conducted during the past 10 years was retrieved through MEDLINE and critically evaluated. Animal and human studies suggest potential benefits of dietary modification, exercise, antioxidants, hormones, and deprenyl. Due to the interrelationships between disease and older age and the limitations of existing research in this area, most life extension strategies are untested hypotheses. Many strategies merit scientific inquiry, but they cannot be recommended for use. More extensive research is necessary to assess their safety, effectiveness, and socioeconomic impact, and to resolve ethical controversies before they can be considered applicable in humans.