Preventing instability of the Taylor Spatial Frame (TSF) during a strut change

SUMMARY: During treatment with a Taylor Spatial Frame, some of the struts may need to be exchanged for one of a different length. An extra "seventh" strut is usually added to the frame during this procedure. This article describes a "technical trick" to ensure stability during a strut change. The frame was stable whenever the orientation of the "acute ring-strut" of the temporary strut matched that of the strut being exchanged. Clinicians must anticipate that instability can exist during strut changes, and this will depend on the particular configuration and position of the frame. Applying the rule indentified in this article may prevent instability, pain, and tissue damage.     

Subjective and objective incontinence 5 to 10 years after Burch colposuspension

The outcome of incontinence surgery was studied using a questionnaire, a 24-hour pad test (24hPT), and a stress test (ST). Five to 10 years after a Burch colposuspension, 111 patients were asked to complete the Bristol Female Urinary Tract Symptom Questionnaire (BFLUTS) and to perform a 24hPT and a ST. Eighty-two patients completed the questionnaire and 71 and 69 patients performed the stress and pad tests, respectively. Seventy-three percent of the patients did not leak during the ST and 75% of the patients were not leaking during the 24hPT. Seventy-three percent of the patients stated that they were at least occasionally stress or urge incontinent and 62% stated that they were both stress and urge incontinent. However, only 24% of the stress incontinent and 28% of the urge incontinent patients found their incontinence to be "quite a problem" or "a serious problem." Patients leaking urine only "occasionally," "once a week," leaking "drops," and finding the leakage to be "a bit of a problem" had median leakage 0g during ST and 24hPT. Patients who reported the leakage to occur "sometimes" "most or all of the time" and who found the leakage to be "a bit, quite, or a serious problem" accounted for 20 to 30% of all patients, as did patients leaking during objective tests. Objective tests revealed leakage to occur less frequently compared with self-reported leakage. The BFLUTS questionnaire revealed leakage to occur with varying frequency, amount, and bother. Leakage occurring seldom, of small amount and bother may be of minor clinical importance.     

Short-term perfusion and “Equilibration” of canine kidneys with protective solutions

Summary Kidneys were perfused either with Euro-Collinssolution or with HTK-solution of Bretschneider. The perfusion pressure as well as the perfusion flow were measured during a six-minute perfusion. The perfusion resistance was higher in Euro-Collins-kidneys than during HTK-perfusion. The venous outflow of the kidney as well as the ureteral outflow was measured during each minute of the perfusion and has analysed for osmolality, and for sodium and potassium concentrations. In Euro-Collins-kidneys a complete equilibration of the extracellular space was not achieved, while during HTK-perfusion concentrations in the venous as in the tubular outflow, similar to those in the HTK-solution itself, could be reached. At the end of the different perfusions, tissue was analysed for biochemical parameters such as ATP, ADP, AMP and lactate as well as for morphological features. Lactate had increased and ATP had decreased during perfusion with Euro-Collins-solution, while ATP had not changed and lactate had decreased during perfusion with HTK-solution. Normal glomerular, tubular and dilated vascular structures can be seen after HTK-perfusion, while a glomerular and vascular contraction takes place during Euro-Collins-perfusion.Supported by the Deutsche Forschungsgemeinschaft, SFB 89-Kardiologie Göttingen     

Sacral nerve stimulation for fecal incontinence and constipation in adults: a short version Cochrane review

BACKGROUND: Fecal incontinence and constipation are disabling conditions that reduce quality of life. If conservative treatment fails, one option is sacral nerve stimulation (SNS), a minimally invasive technique allowing modulation of the nerves and muscles of the pelvic floor and hindgut. OBJECTIVES: To assess the effects of SNS for fecal incontinence and constipation in adults. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialized Trials Register (searched 24 April 2007) and the reference lists of relevant articles. SELECTION CRITERIA: All randomized or quasi-randomized trials assessing the effects of SNS for fecal incontinence or constipation in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results, assessed the methodological quality of the included studies, and undertook data extraction. MAIN RESULTS: Three crossover studies were included. Two, enrolling 34 (Leroi) and two participants (Vaizey), assessed the effects of SNS for fecal incontinence, and one (Kenefick), enrolling two participants, assessed SNS for constipation.In the study by Leroi, following the crossover period, participants, while still blinded, chose the period of stimulation they had preferred. Outcomes at different time points were reported separately for 19 participants who preferred the "on" and five who preferred the "off" period. For the group of 19, the median (range) episodes of fecal incontinence per week fell from 1.7 (0-9) during the "off" period to 0.7 (0-5) during the "on" period; for the group of five, however, the median (range) rose from 1.7 (0-11) during the "off" period compared with 3.7 (0-11) during the "on" period. Vaizey reported an average of six, and one, episodes of fecal incontinence per week during the "off" and "on" periods, respectively. Leroi reported that four of 27 participants experienced an adverse event resulting in removal of the stimulator; Vaizey did not report adverse events.For SNS for constipation, during the "off" crossover period the participants experienced an average of two bowel movements per week, compared with five during the "on" period. Abdominal pain and bloating occurred 79% of the time during the "off" period compared with 33% during the "on" period. No adverse events occurred. AUTHORS' CONCLUSIONS: The very limited evidence from the included studies suggests that SNS can improve continence in selected people with fecal incontinence, and reduce symptoms in selected people with constipation. However, temporary, percutaneous stimulation for a 2-3-week period does not always successfully identify those for whom a permanent implant will be beneficial. Larger, good quality randomized crossover trials are needed to allow the effects of SNS for these conditions to be assessed with more certainty.     

Regulation of respiration in assisted ventilation

Based on knowledge of the control of external respiration, the physiological reactions are discussed which should be evoked proprioceptively and chemoreceptively by an assisting respirator's disturbances of spontaneous breathing movements. The following possible states are discriminated: 1. "no adaption": the respiratory motor system does not remain passive during the machine's stroke; 2. "passive adaption": the respiratory motor system remains passive during the respirator's stroke; to changes of the blood gas-status, only the breathing frequency responds, but in just the same manner as during spontaneous ventilation; 3. "active adaption": the ventilatory motor apparatus remains passive during the respirator's operation; changes of the blood gases are responded to by the breathing frequency only, but in a manner different to spontaneous breathing and which compensates for the invariability of the fixed stroke-volume. - Related to these 3 states, consequences concerning the efficiency of chemical respiratory control can be derived which should reveal themselves during experimental manipulation of the blood gas partial pressures. Accordingly, the CO2-response curves of minute ventilation, breathing frequency and tidal-volume generated in 9 healthy, awake and cooperative subjects during spontaneous breathing and assisted (stroke-volume controlled) respiration with gas mixtures of 0, 3 and 6% CO2 were investigated and compared. (In each subject assisted ventilation with 2 or 3 different stroke-volumes was performed. The smallest stroke-volume equalled the medium tidal-volume of spontaneous ventilation. Every stroke-volume produced its particular CO2-response curve). Hence it follows that with assisted ventilation, using a stroke-volume larger than the spontaneous tidal-volume, the subjects maintain a state between "passive" and "active adaption".(ABSTRACT TRUNCATED AT 250 WORDS)     

RETRACTED ARTICLE: Reduction of postoperative nausea and vomiting with granisetron

The antiemetic effects of granisetron, a selective 5-hydroxy-tryptamine type 3 receptor antagonist, on postoperative nausea and vomiting were studied and compared with placebo and metoclopramide in 60 patients undergoing general anaesthesia for major gynaecological surgery. The patients received a single iv dose of either granisetron (3 mg, n = 20) metoclopramide (10 mg, n = 20), or placebo (saline, n = 20) immediately after recovery from anaesthesia. The effects were assessed during the first three and the next 21 hr after recovery from anaesthesia by means of a nausea and vomiting score; 0 = no emetic symptoms, 1 = nausea, 2 = vomiting. The mean scores during 0–3 hr were 0.8, 0.1 and 0.1 after administration of placebo, metoclopramide and granisetron, respectively; the corresponding scores during 3–24 hr were 0.6, 0.5 and 0.1. The scores of the metoclopramide and the granisetron groups were different from the placebo group in the first three hours (P < 0.05). Although there were no differences in the scores during 0–3 hr between the metoclopramide and the granisetron groups, there were differences during 3–24 hr (P < 0.05). It is concluded that granisetron is superior to metoclopramide in the long-term prevention of postoperative nausea and vomiting after anaesthesia.     

Extraction bradycardia: a pilot case-crossover study

Purpose

Significant vasovagal reaction is one of the untoward events in the course of simple extractions. The present study then aimed to record the patients’ heart rate during the extraction procedure.

Materials and methods

Informed consents were obtained in advance. Patients were placed in the dental chair and their heart rate was measured before /and prior to the anesthetic injection, during, and after dental extraction on a pulse oxymeter device. Data were analyzed using paired t-test.

Results

Sixty one patients were included. The mean heart rates of these patients prior, during, and after extraction were 88, 86 and 81, respectively. Two by two comparisons showed a significant decrease in the mean heart rate during extraction compared to the baseline and also after extraction compared to both before and during extraction (p?<?0.05 for all three).

Conclusions

Despite the presence of sufficient local anesthesia and performing the extraction with the least trauma, a significant decrease in heart rate is evident.

     

Decreased antibody-dependent cellular cytotoxicity in minimal change nephrotic syndrome

Secondary IgG response to a tetanus toxoid booster and in vitro measurement of immunoglobulin synthesis, antibody-dependent cellular cytotoxicity (ADCC) and -interferon (IFN-) production were evaluated in 20 healthy controls and in 17 children with minimal change nephrotic syndrome (MCNS), during the acute nephrotic phase and 6 months after remission. Defective responses were observed in all but IFN- production during the acute nephrotic phase; these improved with disease remission. There was a significant correlation between decreases in vitro IgG production and ADCC reaction. These data indicate that defective antibody production is associated with decreased ADCC during the acute nephrotic phase of MCNS.     

Effect of positive end expiratory pressure on arterial oxygenation during bronchoalveolar lavage for proteinosis

To maintain good cellular oxygenation during bronchopulmonary lavage for alveolar proteinosis is often a difficult problem to solve. A case is reported of alveolar proteinosis in whom four lavages were performed. Details of the technique are discussed, as are the problems with expedients used to improve PaO2. The use of a 10 cmH2O positive end-expiratory pressure was useful only during the "in-phase"; in the "out-phase", it worsened the PaO2. PaO2 during lavage in patients with alveolar proteinosis can only be improved by three ways: cancellation of the shunt during lung filling and, during the "out-phase", an increase in FIO2 or pulmonary artery occlusion by a balloon.     

Brain activation during working memory is altered in patients with type 1 diabetes during hypoglycemia

OBJECTIVE

To investigate the effects of acute hypoglycemia on working memory and brain function in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS

Using blood oxygen level–dependent (BOLD) functional magnetic resonance imaging during euglycemic (5.0 mmol/L) and hypoglycemic (2.8 mmol/L) hyperinsulinemic clamps, we compared brain activation response to a working-memory task (WMT) in type 1 diabetic subjects (n = 16) with that in age-matched nondiabetic control subjects (n = 16). Behavioral performance was assessed by percent correct responses.

RESULTS

During euglycemia, the WMT activated the bilateral frontal and parietal cortices, insula, thalamus, and cerebellum in both groups. During hypoglycemia, activation decreased in both groups but remained 80% larger in type 1 diabetic versus control subjects (P < 0.05). In type 1 diabetic subjects, higher HbA_1c was associated with lower activation in the right parahippocampal gyrus and amygdala (R² = 0.45, P < 0.002). Deactivation of the default-mode network (DMN) also was seen in both groups during euglycemia. However, during hypoglycemia, type 1 diabetic patients deactivated the DMN 70% less than control subjects (P < 0.05). Behavioral performance did not differ between glycemic conditions or groups.

CONCLUSIONS

BOLD activation was increased and deactivation was decreased in type 1 diabetic versus control subjects during hypoglycemia. This higher level of brain activation required by type 1 diabetic subjects to attain the same level of cognitive performance as control subjects suggests reduced cerebral efficiency in type 1 diabetes.Acute episodes of hypoglycemia are a rate-limiting adverse effect in the treatment of type 1 diabetes. When severe, they can lead to seizures and coma (1). Even mild to moderate hypoglycemia is known to impair cognitive functions, such as working memory (2,3). Working memory is used to actively maintain and manipulate information over a brief period of time and to allocate attentional resources among competing subtasks (4,5). Traditionally, working-memory performance is thought to depend primarily on a network of brain regions, including portions of the frontal and parietal lobes, thalamus, precuneus, cerebellum, and insula (6,7).Using blood oxygen level–dependent (BOLD) functional magnetic resonance imaging (fMRI), we evaluated how diabetes impacts these neural processes under euglycemic and hypoglycemic conditions when subjects were presented with a working-memory task (WMT). Diabetes is known to negatively affect working memory (8). This task evaluates functional effects that might reflect changes in brain structure and/or presage decreases in cognitive performance. A better understanding of the brain’s metabolic and physiological mechanisms underlying the cognitive functions implicated in working memory could lead to improved treatment strategies to help maintain cortical function in patients with diabetes during hypoglycemia (9).BOLD fMRI is a well-established method for examining regional brain activation in response to physiological, pharmacological, sensory, or cognitive tasks (10). Studies that have examined brain activation in response to sensory stimulation or cognitive challenges using BOLD fMRI during hypoglycemic conditions in nondiabetic subjects (11–13) have shown that hypoglycemia reduces regional brain BOLD activation. This reduction in BOLD response during hypoglycemia has been attributed to low glucose levels causing decreases in neuronal activity, glucose oxidative metabolism, cerebral blood flow, neurovascular coupling, and/or neuronal recruitment (12).Whether cognitive function in patients with type 1 diabetes is affected by hypoglycemia in the same manner as in nondiabetic individuals remains unclear because few studies using functional neural imaging have directly compared diabetic and nondiabetic subjects during the performance of cognitive tasks (14,15). If brain glucose transport or metabolism are altered in type 1 diabetes, as has been suggested in recent studies by our group (16) and others (17), then one would expect that the BOLD activation response during hypoglycemia may differ between diabetic patients compared with nondiabetic control subjects. On the basis of these findings, we hypothesized that 1) patients with type 1 diabetes would have greater BOLD activation during the performance of a WMT during hypoglycemia when compared with nondiabetic control subjects, 2) cognitive performance would deteriorate during hypoglycemia in both groups, and 3) among type 1 diabetic patients, better glycemic control (lower HbA_1c) would correlate with BOLD activation responses to the WMT during hypoglycemia. We also conducted exploratory analyses to examine deactivation patterns in the default-mode network (DMN), the regions of the brain that are more active during rest (18), because of other research by our group examining the effects of diabetes on deactivation patterns during cognitive tasks and previous research suggesting that DMN function may be altered in diseases that affect cognition, such as Alzheimer’s disease (19).     

The effect of positive end expiratory pressure on rebreathing and gas dilution in the Ayre's T-piece system--a laboratory study.

The effect of positive end expiratory pressure on the function of the Ayre's T-Piece System was studied using a simple lung model. Positive end expiratory pressure did not effect end tial CO2 during "controlled breathing" but caused an increase during "spontaneous breathing" when fresh gas flow was less than 3 times the minute volume. Gas dilution did not occur under any of the test conditions.     

Subarachnoidal Block after a "Top-up" Dose during Continuous Segmental Epidural Analgesia in Labour a Case Report

We describe a case of spinal block which developed after a second "top-up" of local anaesthetic during segmental epidural analgesia in labour. The incidence of similar cases is reviewed. The importance of aspiration and the injection of a "test" dose before every "top-up" is stressed.     

Effects of Antecedent GABAA Activation With Alprazolam on Counterregulatory Responses to Hypoglycemia in Healthy Humans

OBJECTIVE

To date, there are no data investigating the effects of GABA_A activation on counterregulatory responses during repeated hypoglycemia in humans. The aim of this study was to determine the effects of prior GABA_A activation using the benzodiazepine alprazolam on the neuroendocrine and autonomic nervous system (ANS) and metabolic counterregulatory responses during next-day hypoglycemia in healthy humans.

RESEARCH DESIGN AND METHODS

Twenty-eight healthy individuals (14 male and 14 female, age 27 ± 6 years, BMI 24 ± 3 kg/m², and A1C 5.2 ± 0.1%) participated in four randomized, double-blind, 2-day studies. Day 1 consisted of either morning and afternoon 2-h hyperinsulinemic euglycemia or 2-h hyperinsulinemic hypoglycemia (2.9 mmol/l) with either 1 mg alprazolam or placebo administered 30 min before the start of each clamp. Day 2 consisted of a single-step hyperinsulinemic-hypoglycemic clamp of 2.9 mmol/l.

RESULTS

Despite similar hypoglycemia (2.9 ± 1 mmol/l) and insulinemia (672 ± 108 pmol/l) during day 2 studies, GABA_A activation with alprazolam during day 1 euglycemia resulted in significant blunting (P < 0.05) of ANS (epinephrine, norepinephrine, muscle sympathetic nerve activity, and pancreatic polypeptide), neuroendocrine (glucagon and growth hormone), and metabolic (glucose kinetics, lipolysis, and glycogenolysis) counterregulatory responses. GABA_A activation with alprazolam during prior hypoglycemia caused further significant (P < 0.05) decrements in subsequent glucagon, growth hormone, pancreatic polypeptide, and muscle sympathetic nerve activity counterregulatory responses.

CONCLUSIONS

Alprazolam activation of GABA_A pathways during day 1 hypoglycemia can play an important role in regulating a spectrum of key physiologic responses during subsequent (day 2) hypoglycemia in healthy man.Hypoglycemia continues to be the major limiting factor to good glycemic control in patients with diabetes. During the last two decades, there have been many studies demonstrating that antecedent hypoglycemia can blunt counterregulatory responses to subsequent hypoglycemia in healthy and type 1 and type 2 diabetic individuals (1). Despite the clinical importance and many elegant studies addressing this topic, there remain gaps in our knowledge regarding the mechanisms regulating neuroendocrine and autonomic nervous system (ANS) responses during episodes of repeated hypoglycemia in man.The three major acute neuroendocrine/ANS counterregulatory defenses against a falling plasma glucose include release of glucagon and epinephrine combined with inhibition of endogenous insulin release. All of these mechanisms either fail (i.e., insulin modulation and glucagon release within ∼5 years of type 1 diabetes duration) or become substantially reduced with disease duration (type 2 diabetes). Furthermore, repeated hypoglycemia has been demonstrated to reduce epinephrine and glucagon responses, which are important defenses against subsequent falling blood glucose levels in both type 1 (epinephrine) and type 2 (epinephrine and glucagon) diabetes (2).For many years, the problem of severe or frequent hypoglycemia was thought to be confined almost exclusively to type 1 diabetes. Recent multicenter trials aimed at improving glycemic control both within hospitals and in the community have identified excess adverse events and death plausibly related to hypoglycemia in type 2 diabetes (3,4). The glucagon response to hypoglycemia is initially relatively preserved in type 2 diabetes (although there is decrease with disease duration) (5). However, as the prevalence of hypoglycemia is increasing in type 2 diabetes, it continues to be of importance to understand the mechanisms regulating release of both glucagon and epinephrine during repeated episodes of hypoglycemia.γ-Aminobytyric acid (GABA) is a major inhibitory neurotransmitter. Previous studies have demonstrated increases in GABAergic tone within the ventromedial hypothalamus in rats with repeated hypoglycemia, which is associated with blunted glucagon and epinephrine responses (6). Chan et al. (7) have also demonstrated that blockade of GABA_A receptors within the ventromedial hypothalamus in rats results in increased glucagon and epinephrine responses during hypoglycemia. Studies investigating the effects of GABA_A modulation on counterregulatory responses during hypoglycemia in humans are scarce. In fact, previous studies have used activation of GABA_A receptors rather than changes in GABA concentrations to investigate the role of GABAergic pathways in ANS and neuroendocrine counterregulatory responses during hypoglycemia in humans and primates. van Vugt et al. (8) demonstrated that alprazolam (a potent pharmacologic activator of the benzodiazepine-GABA_A receptor) can inhibit anterior pituitary neuroendocrine responses during acute hypoglycemia in rhesus monkeys. Giordano et al. (9) reported that alprazolam also reduced neuroendocrine and epinephrine responses to acute intravenous insulin bolus–induced hypoglycemia in healthy humans. Breier et al. (10), using a model of 2-deoxyglycose–induced glucoprivic stress in humans, also demonstrated that alprazolam blunted ACTH and epinephrine responses during neuroglycopenia. Lastly, Smith et al. (11), using modafinil to acutely lower GABA levels during clamped hypoglycemia in healthy humans, reported increased heart rate and improved cognitive function with the drug. Thus, available data would indicate that GABA_A activation can acutely reduce, whereas GABA_A blockade can increase, neuroendocrine and sympathoadrenal responses to hypoglycemia. However, it is unknown whether GABA_A activation can play a mechanistic role in causing neuroendocrine and ANS failure during repeated hypoglycemia in healthy humans. Therefore, in the present study, we have tested the hypothesis that antecedent pharmacologic activation of benzodiazepine-GABA_A receptors with alprazolam can result in counterregulatory failure during next-day hypoglycemia in healthy humans.     

Protein catabolism in advanced renal disease: role of cytokines

BACKGROUND: Protein energy wasting is a maladaptive metabolic state often associated with inflammation, which is common in patients with chronic kidney disease (CKD). METHODS: A literature search was performed using MEDLINE and the reference lists of relevant review articles. The following key words were used in the MEDLINE search: "cytokines", "inflammation", "protein metabolism", "acute-phase protein", "cachexia", "chronic kidney disease", "end-stage renal disease" and "hemodialysis". The search was limited to English-language articles. RESULTS: While experimental models have shown that uremic animals are more prone for proteolysis, the results from the human studies are controversial. Intradialytic loss of amino acids and activation of proinflammatory cytokines lead to protein catabolism during hemodialysis (HD). At the whole-body level, intradialytic parenteral nutrition (IDPN) increases protein synthesis and decreases proteolysis. Amino acid infusion during HD increases muscle protein synthesis, but does not decrease protein catabolism. Activation of interleukin-6 during HD induces protein catabolism, impairs amino acid utilization for protein synthesis and increases acute-phase protein synthesis. CONCLUSION: The changes in albumin, fibrinogen and muscle protein kinetics during HD could be due to competing and complementary effects of availability of amino acids and activation of proinflammatory cytokines.     

Fundus-first laparoscopic cholecystectomy

Removal of the gallbladder with commencement of dissection at the fundus is well recognized as a safe technique during difficult open cholecystectomy because it minimizes the risks of damage to the structures in or around Calot's triangle. We report here the routine employment of liver retractors and fundus-first dissection during laparoscopic cholecystectomy (LC) as an alternative to techniques previously described.Retraction of the liver and fundus-first dissection was used in 53 patients who underwent laparoscopic cholecytectomy. There were 16 male and 37 female patients. Seven were operations performed during an acute admission and 20 had moderate or severe adhesions involving the gallbladder. Thirteen patients had a preexisting abdominal incision.The procedure was successful in 52 patients (98%), but in one patient it was converted to open operation because of dense adhesions. Median duration of operation was 90 min (range 35–240 min). There was no mortality and two complications (persistent right upper quadrant pain for 2 weeks after operation and bile leakage from the gallbladder bed).The facility to retract the liver and carry out a fundus-first dissection extends techniques developed for open surgery into the laparoscopic arena. It offers the surgeon the safety and versatility during laparoscopic cholecystectomy that it confers during conventional open surgery.Presented at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons (SAGES), Nashville, Tennessee, USA, 18–19 April 1994     

Lipid-Induced Insulin Resistance Is Not Mediated by Impaired Transcapillary Transport of Insulin and Glucose in Humans

Increased lipid availability reduces insulin-stimulated glucose disposal in skeletal muscle, which is generally explained by fatty acid–mediated inhibition of insulin signaling. It remains unclear whether lipids also impair transcapillary transport of insulin and glucose, which could become rate controlling for glucose disposal. We hypothesized that lipid-induced insulin resistance is induced by inhibiting myocellular glucose uptake and not by interfering with the delivery of insulin or glucose. We measured changes in interstitial glucose and insulin in skeletal muscle of healthy volunteers during intravenous administration of triglycerides plus heparin or glycerol during physiologic and supraphysiologic hyperinsulinemia, by combining microdialysis with oral glucose tolerance tests and euglycemic-hyperinsulinemic clamps. Lipid infusion reduced insulin-stimulated glucose disposal by ∼70% (P < 0.05) during clamps and dynamic insulin sensitivity by ∼12% (P < 0.05) during oral glucose loading. Dialysate insulin and glucose levels were unchanged or even transiently higher (P < 0.05) during lipid than during glycerol infusion, whereas regional blood flow remained unchanged. These results demonstrate that short-term elevation of free fatty acids (FFAs) induces insulin resistance, which in skeletal muscle occurs primarily at the cellular level, without impairment of local perfusion or transcapillary transport of insulin and glucose. Thus, vascular effects of FFAs are not rate controlling for muscle insulin-stimulated glucose disposal.Skeletal muscle accounts for the majority of glucose uptake after a meal and almost all glucose disposal during hyperinsulinemic-euglycemic clamps (1). In type 2 diabetes (T2DM), muscle insulin resistance predicts postprandial hyperglycemia, but the underlying mechanisms are unclear. Insulin-resistant humans frequently present with increased plasma free fatty acids (FFAs) (2), which can give rise to myocellular diacylglycerols or ceramides and impair insulin signaling (3–5). Insulin increases muscle microvascular perfusion and facilitates delivery of nutrients and hormones to the interstitium (6). Animal models of lipid-induced insulin resistance suggest that insulin-mediated microvascular perfusion is already reduced in prediabetic states and relates to impaired insulin action (7,8). Preventing the access of glucose and insulin to myocytes could contribute to lower glucose disposal and place abnormal microvascular insulin action as an early event in the development of T2DM.We hypothesized that lipid-induced insulin resistance results from myocellular glucose uptake, but not from impaired delivery of insulin or glucose to the interstitium. We monitored changes of interstitial insulin and glucose in muscle of humans during intravenous triglycerides or glycerol administration under physiologic dynamic (oral glucose tolerance test [OGTT]) and supraphysiologic constant hyperinsulinemic (clamp) conditions.     

Determinants of change in bone mineral density and fracture risk during bisphosphonate holiday

Summary

In a retrospective analysis of 208 osteoporotic patients followed during a bisphosphonate holiday, lower body weight and risedronate use were associated with a more rapid decline in bone mineral density during the bisphosphonate holiday, while bone mineral density (BMD) trends were similar in patients who sustained vs. did not sustain a fracture.

Introduction

A drug holiday has been suggested for some bisphosphonate-treated patients with osteoporosis to minimize potential side effects from prolonged use. However, there is limited information on the evolution of BMD during a bisphosphonate holiday. Our study analyzed the longitudinal course of BMD following bisphosphonate discontinuation and assessed its determinants.

Methods

Retrospective single-center cohort study of osteoporosis patients treated with alendronate or risedronate for at least 2 years and then discontinued their bisphosphonate for a drug holiday. Patients were stratified by bisphosphonate type and by fracture occurrence during drug holiday.

Results

A total of 208 patients were included in this analysis (87.5 % female). At the time of bisphosphonate cessation, mean?±?SD age was 66.9?±?8.9 years and BMI 24.5?±?4.4 kg/m². Duration of bisphosphonate treatment was 5.2?±?2.3 years, and follow-up during holiday was 3.3?±?1.7 years. During the first 2 years of the holiday, BMD remained stable at the lumbar spine and femoral neck, but declined significantly at the total hip. BMD declined significantly at all sites thereafter. Significant predictors of BMD decline during bisphosphonate holiday included lower BMI at the start of the holiday and change in body weight during the holiday. BMD decline was more pronounced in former risedronate compared to former alendronate users. BMD trends were similar in patients who sustained vs. did not sustain a fracture during the holiday.

Conclusions

BMD at the total hip declines significantly within 1 year of bisphosphonate discontinuation, particularly in lean patients. Additional studies are needed to identify predictors of fracture incidence during a bisphosphonate holiday.

     

"Splint dishabituation" in treatment of distal injuries of the digital extensor tendons

Results of treatment of 61 patients with "mallet finger" injuries have been analyzed. After discontinuation of permanent immobilization the patients of the main group (n = 20) underwent "splint dishabituation" consequentially and bit by bit during 8 weeks, according to an original protocol developed with special reference to the stages of biological process of union of the damaged tendon. Following permanent immobilization patients of the group of comparison (n = 35) were recommended to use a removable splint at night during two weeks. The proposed protocol of "splint dishabituation" improved the results of treatment of injuries of the "mallet finger" type.     

Defining Quackery: an examination of the Manitoba Medical Profession and the early development of professional unity

In the early 1920s, the Manitoba medical profession reached a pinnacle in its opposition to alternative medicine, waging an aggressive four-year campaign against chiropractic and osteopathy to "protect" the public from the dangers of alternative forms of healing and prevent "irregulars" from establishing their practices. It was during these same years that the Manitoba medical profession was able to successfully overcome many internal problems of consensus and external problems of legitimacy. Examining the years leading up to, during, and following the campaign, this paper demonstrates how the Manitoba medical profession's militant reaction to osteopathy and chiropractic during these years helped strengthen and differentiate orthodox practitioners as a group, thus reinforcing their authority within the public realm.