Long-term trajectories of bone metabolism parameters and bone mineral density (BMD) in obese patients treated with metabolic surgery: a real-world, retrospective study.

PURPOSE: Potential negative effects of metabolic surgery on skeletal integrity remain a concern, since long-term data of different surgical approaches are poor. This study aimed to describe changes in bone metabolism in subjects with obesity undergoing both Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). METHODS: A single center, retrospective, observational clinical study on real-world data was performed enrolling subjects undergoing metabolic surgery. RESULTS: 123 subjects were enrolled (males 31: females 92; ages 48.2 ± 7.9 years). All patients were evaluated until 16.9 ± 8.1 months after surgery, while a small group was evaluated up to 4.5 years. All patients were treated after surgery with calcium and vitamin D integration. Both calcium and phosphate serum levels significantly increased after metabolic surgery and remained stable during follow-up. These trends did not differ between RYGB and SG (p = 0.245). Ca/P ratio decreased after surgery compared to baseline (p < 0.001) and this decrease remained among follow-up visits. While 24-h urinary calcium remained stable across all visits, 24-h urinary phosphate showed lower levels after surgery (p = 0.014), also according to surgery technique. Parathyroid hormone decreased (p < 0.001) and both vitamin D (p < 0.001) and C-terminal telopeptide of type I collagen (p = 0.001) increased after surgery. CONCLUSION: We demonstrated that calcium and phosphorous metabolism shows slight modification even after several years since metabolic surgery, irrespective of calcium and vitamin D supplementation. This different set point is characterized by a phosphate serum levels increase, together with a persistent bone loss, suggesting that supplementation alone may not ensure the maintenance of bone health in these patients.

Randomised, double-blind, placebo-controlled, assessment of the efficacy and safety of dietary supplements in prehypertension.

We aimed to evaluate efficacy and tolerability of a protocol including lifestyle modifications and a novel combination of dietary supplements in prehypertension. A prospective, double-blind, randomised, placebo-controlled trial was conducted in 176 subjects (103 men, aged 52±10 years), with blood pressure (BP) of 130-139 mm Hg systolic and/or 85-89 mm Hg diastolic entered. After a single-blind run-in period, participants were randomised to twice daily placebo (n=88) or a commercially available combination pill (n=88). Primary endpoints were the differences in clinic BP between the two groups at the end of the trial. Secondary endpoints included intragroup differences in clinic BP during the study period and response rates (that is, BP <130/85 mm Hg or a BP reduction >5 mm Hg on week 12). Baseline characteristics were similar among the treatment groups. At 12 weeks, the supplement group had lower systolic BP (124±9 versus 132±7 mm Hg, P<0.0001) and similar diastolic BP (81±8 versus 82±7 mm Hg, P=0.382) compared to the placebo group. With respect to baseline measures, changes in BP with supplements were statistically significant for systolic (-9.3±4.2 mm Hg, P<0.0001) and diastolic values (-4.2±3.6 mm Hg, P<0.0001). Changes versus baseline in systolic and diastolic BP, conversely, were not different on placebo. The overall response rate at week 12 was significantly greater with supplements than placebo (58% (51 of 88) and 25% (22 of 88), respectively, P<0.0001). This randomised trial shows that combination of supplements with BP-lowering effect is an effective additional treatment to conventional lifestyle modifications for a better control of systolic BP in prehypertension.

Acupuncture for systemic lupus erythematosus: a pilot RCT feasibility and safety study.

The objective of this study was to determine the feasibility of studying acupuncture in patients with systemic lupus erythematosus (SLE), and to pilot test the safety and explore benefits of a standardized acupuncture protocol designed to reduce pain and fatigue. Twenty-four patients with SLE were randomly assigned to receive 10 sessions of either acupuncture, minimal needling or usual care. Pain, fatigue and SLE disease activity were assessed at baseline and following the last sessions. Safety was assessed at each session. Fifty-two patients were screened to enroll 24 eligible and interested persons. Although transient side effects, such as brief needling pain and lightheadedness, were reported, no serious adverse events were associated with either the acupuncture or minimal needling procedures. Twenty-two participants completed the study, and the majority (85%) of acupuncture and minimal needling participants were able to complete their sessions within the specified time period of 5-6 weeks. 40% of patients who received acupuncture or minimal needling had >/=30% improvement on standard measures of pain, but no usual care patients showed improvement in pain. A ten-session course of acupuncture appears feasible and safe for patients with SLE. Benefits were similar for acupuncture and minimal needling.

Calpain III mutation analysis of a heterogeneous limb-girdle muscular dystrophy population.

OBJECTIVE: To determine the frequency of calpain III mutations in a heterogeneous limb-girdle muscular dystrophy (LGMD) population. BACKGROUND: Mutations of the calpain III gene have been shown to cause a subset of autosomal recessive LGMDs. Patient populations studied to date have been primarily of French and Spanish origin, in which calpain III may cause 30% of autosomal recessive MDs. The incidence of calpain III mutations in non-French/Spanish MD patients has not been studied thoroughly. No sensitive and specific biopsy screening methods for detecting patients with abnormal calpain III protein are available. Thus, detection of patients relies on direct detection of gene mutations. METHODS: The authors studied the calpain III gene in 107 MD patient muscle biopsies exhibiting normal dystrophin. Muscle biopsy RNA was produced for each patient, and the entire calpain III complementary DNA was screened for mutations by reverse-transcriptase PCR/single-strand conformation polymorphism using three different conditions. RESULTS: The authors identified nine patients (eight unrelated) with causative mutations. Six of the seven distinct mutations identified are novel mutations and have not been described previously. CONCLUSION: The results suggest that approximately 9.2% of patients in the heterogeneous population with an LGMD diagnosis will show mutations of the calpain III gene. Interestingly, two patients were heterozygous for a single mutation at the DNA level, whereas only the mutant allele was observed at the RNA level. This suggests that there are undetectable, nondeletion mutations that ablate expression of the calpain III gene.

Traumatic onset of temporomandibular disorders: positive effects of a standardized conservative treatment program.

OBJECTIVE: To compare presenting problems and response to treatment of chronic temporomandibular (TMD) patients who perceive the onset of their symptoms to be related to trauma with those who report symptoms of unknown origin. DESIGN: Prospective treatment outcome study. SETTING: Outpatient multidisciplinary pain treatment center at a university medical center. PATIENTS: A total of 361 were evaluated initially, including 103 who perceived traumatic onset of symptoms and 258 who did not perceive onset to be related to trauma. Two hundred thirty-three (59 trauma and 174 nontrauma) returned for follow-up evaluation 6 months after the conclusion of treatment. INTERVENTIONS: Standardized six-session treatment program consisting of intraoral appliance, biofeedback, and stress management training. OUTCOME MEASURES: Clinical changes in muscle pain, temporomandibular joint pain, and mandibular opening. Self-report of change in perceived pain severity (MPQ--short form), depressive symptoms (BDI), catastrophizing about pain (CSQ--catastrophizing scale), MPI--interference scale, oral parafunctional habits, global evaluation of improvement, and use of pain medications at follow-up. RESULTS AND CONCLUSIONS: Regression of onset type on pretreatment variables indicated that a small but statistically significant proportion of pretreatment variability (8.7%) could be accounted for by onset. Both traumatic and nontraumatic onset groups showed positive outcomes following treatment. No significant differences between groups were found for any of the clinical or self-reported outcome measures with the exception that a significantly higher percentage of the trauma group reported using pain medication at follow-up. These findings are in contrast with previous suggestions that post-traumatic TMD patients show poorer response to treatment than nontrauma TMD patients.

Elongated styloid process in a temporomandibular disorder sample: prevalence and treatment outcome.

An elongated styloid process is an anatomic anomaly present in 2% to 30% of adults; it is occasionally associated with pain. Its prevalence among patients with classic temporomandibular disorder pain symptoms is unknown. The effect of conservative treatment on patients who have symptoms of temporomandibular disorders and an elongated styloid process is also unknown. The objectives of this study were to determine the prevalence of the elongated styloid process in a sample of patients with temporomandibular disorders and to compare patients with and without the elongated styloid process on initial presenting signs and symptoms and treatment outcome. A total of 100 panoramic radiographs of patients with symptomatic temporomandibular disorders were examined to ascertain the presence or absence of an elongated styloid process. All patients participated in a conservative treatment program of biofeedback and stress management and a flat-plane intraoral appliance. Initial symptoms and treatment outcome of patients with and without an elongated styloid process were compared by use of multivariate analysis of variance on several oral-paraoral and psychosocial-behavioral methods. The prevalence of an elongated styloid process in this clinic sample of temporomandibular disorders was 27%. The patients with or without an elongated styloid process were not significantly different in pretreatment symptoms, and both groups exhibited substantial treatment gains. However, patients with an elongated styloid process showed significantly less improvement on unassisted mandibular opening without pain than did patients who did not have an elongated styloid process. This suggests that an elongated styloid process may place structural limitations on pain-free maximum mandibular opening. The results support conservative management of patients with symptoms of temporomandibular disorders when an elongated styloid process is present.

Dysfunctional patients with temporomandibular disorders: evaluating the efficacy of a tailored treatment protocol.

Forty-eight dysfunctional patients (i.e., high levels of pain, interference, and affective distress and low levels of perceived control) with temporomandibular disorders (TMDs) were randomly assigned either to a treatment consisting of an intraoral appliance (IA) and stress management with biofeedback (SM) plus nondirective, supportive counseling (SC) -- IA + SM + SC -- or to a customized treatment that included cognitive therapy (CT) with the IA and SM--IA + SM + CT. Both treatment groups reported statistically significant reductions on a set of physical, psychosocial, and behavioral measures posttreatment and at a 6-month follow-up. However, the intervention that included CT demonstrated significantly greater reductions in pain, depression, and medication use. Only the groups receiving the treatment that included the CT demonstrated continued improvements to the follow-up on pain associated with muscle palpation, self-reported pain severity, depression, and use of medications. These results support the efficacy of the tailored treatment for dysfunctional TMD.

A simulation model for tumor growth controlled by therapeutic agents.

Results obtained in a controlled tumor growth depend on the experimental model used, the agent employed (drugs, ionizing radiations, heat), aw well as the administration scheduling and the host environment. Empirical search and treatment optimization are related to a discrete number of agent combinations and fractioning, and system parameters and dependencies are strictly connected to biological assumptions. A simplified model for the evaluation of the rate of change of tumor volume at the time of cytotoxic agent administration is proposed here, as well as a computer program to perform the simulation of tumor growth controlled by therapeutic agents.

Enhancement of hyperthermic damage on M14 melanoma cells by liposome pretreatment.

Exponentially growing human melanoma cells (M14 cell line) were pretreated with various amounts of dipalmitoylphosphatidylcholine-containing multilamellar liposomes and then exposed to heat treatment (42.5 degrees C). Cell damage produced by the treatments, given separately or in combination, was evaluated in terms of cell survival. Our results demonstrate that the cell survival at 37 degrees C was not affected by liposome concentrations up to 1000 nmol of phospholipid/2.5 x 10(6) cells, while liposome treatment of cells before heat exposure determined a marked damaging effect even at 100 nmol of phospholipid/2.5 x 10(6) cells. The mechanisms of liposome-cell interaction have been investigated by electron microscopy or by electron spin resonance measurements of spin-labeled membranes of intact cells. Evidence has been obtained that liposomal lipids are either taken up by M14 cells or become incorporated in the cell membrane. The present data suggest the possibility that liposome treatments per se could be of potential value as a therapeutic approach, by increasing the effect of heat therapy.

Monoclonal antibody Tor 23 binds a subset of neural cells in the human cortex and displays an altered binding distribution in Alzheimer's disease.

Recent evidence suggests that alterations in molecules of the external neuronal surface may be pivotal factors in Alzheimer's disease (AD) either as primary or secondary lesions. We are studying neuronal surface components with a library of monoclonal antibodies (MAbs) made to highly purified, exclusively cholinergic nerve terminals of the Torpedo ray. The most extensively characterized of the Tor MAbs. Tor 23, binds the external membrane of some human neuronal cells in culture. Our present findings demonstrate that Tor 23, in situ, binds the apparent limiting membrane of rare neurons of the human isocortex. Tor 23 binds, in addition, internally within a subpopulation of subcortical white matter astrocytes, as identified by colocalization with glial fibrillary acidic protein. Neuronal surface binding of Tor 23 parallels our findings in other species: astrocyte staining was not observed in other species and may be unique to human. Immunoblot analysis of white matter reveals one polypeptide band with a relative mobility of 115,000 +/- 15,000 daltons. In the mid-frontal cortex from cases of AD. Tor 23 immunopositive neurons are greatly reduced in number and immunopositive astrocytes are completely absent. The reduction of the neuronal surface epitope defined by Tor 23 supports the recent hypothesis that surface molecules are altered in AD. The absence of Tor 23 positive astrocytes opens an area for specific investigation: namely, the role subcortical astrocytes may play in the pathogenesis of AD.

Effect of sequential application of hyperthermia and chemotherapy on the survival of a thermoresistant human melanoma cell line.

The human melanoma cell line M14 has been proven in previous experiments to be much less sensitive to the action of heat (42 degrees C, 60 min) than other melanoma lines. In the present study, we have investigated the possibility of increasing the effect of heat by means of drug treatment. Thermochemotherapy was applied to exponentially growing cells according to different schedulings, and was analyzed in its efficacy by measuring the impairment of the cellular colony-forming ability. Findings of the present study point out that: (a) appropriate sequencing between hyperthermia and cis-diamminedichloroplatinum II(DDP), melphalan (L-Pam), 1,2,4-dichlorobenzyl-1H-indazol-3-carboxylic acid (LNA) or 5-3,3-dimethyl-1-triazeno-imidazole-4-carboxamide (DTIC) strongly influences the cytotoxic effect of the two agents; and (b) the optimal combination appears to be the simultaneous application of heat and drugs. However, as far as thermochemotherapy with DDP is concerned, a synergistic effect may also be achieved when hyperthermia precedes DDP.

Kinetic and survival response of the M14 cell line to lonidamine associated with adriamycin or hyperthermia.

Lonidamine (LND), an indazole-carboxylic acid derivative, was delivered alone and together with adriamycin (ADM) or hyperthermia to the human melanoma cell line M14, and cell survival was assessed. Cell cycle-specific effects were investigated by analyzing sequences of DNA content histograms by means of a suitable mathematical procedure. LND delivered for 1 h at a dose of 50 micrograms/ml did not affect proliferation and survival of the cells. Exposure of the cells for 1 h to ADM (1.0 microgram/ml) followed by LND for 1 h (50 micrograms/ml) produced the highest effect on the survival. Kinetic parameters were affected by the combined treatment slightly more than by ADM exposure alone. Simultaneous delivery of LND (50 micrograms/ml) with hyperthermia (42 degrees C, 1 h) reduced the survival and enhanced the block of cells in the G2M phase, as compared with the heat treatment alone. The effect of the treatments on cell survival appeared to be related to the perturbation of the G2M phase of the cycle.