Effect of hyperbaric oxygen therapy on amphotericin-B induced acute renal failure in rats.

AIM: Acute renal injury may occur after amphotericin B (AmB) administration. The hypothesized injury mechanism is renal vasoconstriction and direct toxic damage. Hyperbaric oxygen therapy (HBO) is indicated for treatment of many ischemic events but not for acute renal failure (ARF). The aim of this study was to investigate the role of HBO therapy in AmB induced ARF. METHODS: ARF was induced in 41 Sprague-Dawley rats by a single dose of 75 mg/kg AmB. The rats were randomly divided into two groups; one group was treated with daily HBO for 3 consecutive days. The control group received no HBO treatment. Parameters of renal function were taken on the 5th day after AmB administration. RESULTS: Forty-one rats were treated with AmB, 21 received HBO and 20 served as controls. Body weight loss following the administration of AmB was 13.5+14.7% in the HBO treated rats, as opposed to 24.6+5% in the control group (P=0.004). Serum creatinine and urea were 0.49+0.13 mg/dL and 200.63+87.82 mg/dL in the treatment group and 0.70+0.22 mg/dL and 368.01+169.35 mg/dL, respectively in the control (P=0.001). CONCLUSION: In this model of AmB-induced ARF, HBO treatment alleviated renal injury as reflected by changes in serum creatinine and urea levels.

Vagus nerve stimulation for depression: rationale, anatomical and physiological basis of efficacy and future prospects.

Treatment-resistant depression (TRD) is a major public health concern due to its high costs to society. One of the novel approaches for the treatment of depression is the vagus nerve stimulation (VNS). Therapeutic brain stimulation through delivery of pulsed electrical impulses to the left cervical vagus nerve now has established safety and efficacy as an adjunct treatment for medication-resistant epilepsy and has recently been approved as an adjunct long-term treatment for chronic or recurrent depression. There is considerable evidence from both animal and human neurochemical and neuroimaging studies, that the vagus nerve and its stimulation influence limbic and higher cortical brain regions implicated in mood disorders, providing a rationale for its possible role in the treatment of psychiatric disorders. Clinical studies (open-label and comparator with treatment in naturalistic setting) in patients with TRD have produced promising results, especially when the response rates at longer-term (one- and two-year) follow-up time points are considered. Ongoing research efforts will help determine the place of VNS in the armament of therapeutic modalities available for major depression.

Reduced anterior hippocampal formation volume in hyponatremic schizophrenic patients.

Diminished hippocampal volume occurs in the anterior segment of some schizophrenic patients, and in the posterior segment in others. The significance of hippocampal pathology in general and these segmental differences in specific is not known. Several lines of evidence suggest anterior hippocampal pathology underlies the life-threatening hyponatremia seen in a subgroup of patients with schizophrenia; therefore our goal was to determine if this region was preferentially diminished in hyponatremic patients. We studied seven polydipsic hyponatremic, ten polydipsic normonatremic, and nine nonpolydipsic normonatremic schizophrenic inpatients, as well as 12 healthy controls. All underwent structural scanning on a high resolution (3.0 T) magnetic resonance imaging (MRI) scanner. Hippocampal formation, amygdala, and third ventricle volumes were manually traced in each subject. The hippocampus was divided at the posterior extent of the uncus, and all structural volumes were corrected for whole brain volume and other significant recognized factors (i.e., age, gender, height, parental education). Despite being overhydrated, anterior hippocampal formation volume was diminished in those with polydipsia and hyponatremia relative to each of the other three groups. Third ventricle volume was larger in this group than in healthy controls but similar to the two patient groups. Posterior hippocampal and amygdala volumes did not differ between groups. Other potential confounds (e.g., water imbalance) either had no effect or accentuated these differences. We conclude the anterior hippocampal formation is smaller in hyponatremic schizophrenic patients, thereby linking an important and objective clinical feature of schizophrenia to a neural pathway that can be investigated in animal models. The findings strengthen the hypothesis that anterior hippocampal formation pathology disrupts functional connectivity with other limbic structures in schizophrenia.

Nephrotoxicity of uranyl acetate: effect on rat kidney brush border membrane vesicles.

Since the Gulf war exposure to depleted uranium, a known nephrotoxic agent, there is a renewed interest in the toxic effects of uranium in general and its mechanism of nephrotoxicity which is still largely unknown in particular. In order to investigate the mechanism responsible for uranium nephrotoxicity and the therapeutic effect of urine alkalization, we utilized rat renal brush border membrane vesicles (BBMV). Uranyl acetate (UA) caused a decrease in glucose transport in BBMV. The apparent K (i) of uranyl was 139+/-30 microg uranyl/mg protein of BBMV. Uranyl at 140 microg/mg protein of BBMV reduced the maximal capacity of the system to transport glucose [V (max) 2.2+/-0.2 and 0.96+/-0.16 nmol/mg protein for control and uranyl treated BBMV (P<0.001), respectively] with no effect on the apparent K (m) (1.54+/-0.33 and 1.54+/-0.51 mM for control, and uranyl treated BBMV, respectively). This reduction in V(max) is at least partially due to a decrease in the number of sodium-coupled glucose transporters as apparent from the reduction in phlorizin binding to the uranyl treated membranes, V (max) was reduced from 247+/-13 pmol/mg protein in control BBMV to 119+/-3 pmol/mg protein in treated vesicles (P<0.001). The pH of the medium has a profound effect on the toxicity of UA on sodium-coupled glucose transport in BBMV: higher toxicity at neutral pH (around pH 7.0), and practically no toxicity at alkaline pH (7.6). This is the first report showing a direct inhibitory dose and pH dependent effect of uranyl on the glucose transport system in isolated apical membrane from kidney cortex.

Global structure, robustness, and modulation of neuronal models.

The electrical characteristics of many neurons are remarkably robust in the face of changing internal and external conditions. At the same time, neurons can be highly sensitive to neuromodulators. We find correlates of this dual robustness and sensitivity in a global analysis of the structure of a conductance-based model neuron. We vary the maximal conductance parameters of the model neuron and, for each set of parameters tested, characterize the activity pattern generated by the cell as silent, tonically firing, or bursting. Within the parameter space of the five maximal conductances of the model, we find directions, representing concerted changes in multiple conductances, along which the basic pattern of neural activity does not change. In other directions, relatively small concurrent changes in a few conductances can induce transitions between these activity patterns. The global structure of the conductance-space maps implies that neuromodulators that alter a sensitive set of conductances will have powerful, and possibly state-dependent, effects. Other modulators that may have no direct impact on the activity of the neuron may nevertheless change the effects of such direct modulators via this state dependence. Some of the results and predictions arising from the model studies are replicated and verified in recordings of stomatogastric ganglion neurons using the dynamic clamp.

Treatment of poikiloderma of Civatte on the neck with an intense pulsed light source.

Effective treatment of poikiloderma of Civatte is difficult. The ideal treatment combines elimination of both the vascular and pigmented components simultaneously. Treatment with a broad-spectrum noncoherent intense pulsed light source delivers multiple wavelengths with software-controlled pulse durations and sequencing that permit treatment of both vascular and pigmented lesions simultaneously. The objective of this study was to determine the response and side effects of treating this condition with intense pulsed light. In the study, 66 patients with typical changes of poikiloderma of Civatte on the neck were treated with intense pulsed light at various settings every 4 weeks until the desired improvement occurred. A 50 to 75 percent improvement in the extent of telangiectasias and hyperpigmentation was observed after an average of 2.8 treatments. The incidence of hypopigmentation was 5 percent. It was concluded that intense pulsed light is an effective mode of therapy for poikiloderma of Civatte. It seems to offer a reduction in both pigmentation and telangiectasia-associated erythema, with minimal side effects.

DNA fingerprinting of serial Candida albicans isolates obtained during itraconazole prophylaxis in patients with AIDS.

During a randomized double-blind placebo-controlled study testing the efficacy of itraconazole for prophylaxis of systemic and mucosal fungal infections in patients with acquired immune deficiency syndrome, 298 patients were enrolled with 295 evaluable. Of those, 46 patients were considered prophylaxis failures because of recurrent oral or esophageal candidiasis. Oropharyngeal fungal cultures were taken at the time of suspected thrush or Candida esophagitis, but not at baseline. All of the Candida spp. isolates were cultured on CHROMagar Candida medium then identified using API 20 AUX strips. Antifungal susceptibility testing was performed following the National Committee for Clinical Laboratory Standards M-27A guidelines. Sequential isolates were genotyped using randomly amplified polymorphic DNA. Polymerase chain reaction fingerprints were generated using two repetitive sequence primers, (GGA)7 and (GACA)4. The study group consisted of 23 patients, nine from the itraconazole arm and 14 from the placebo arm, who were prophylaxis failures and had more than two C. albicans isolates. Five of 23 had isolates showing a > or =4-fold reduction in susceptibility; four of these patients were in the itraconazole prophylaxis arm and one was in the placebo arm. Three of the five had yeast isolations showing changes in banding patterns over time. Such changes may indicate genetic changes in the same strain that could be linked to acquired resistance to itraconazole, or acquisition of a new strain, or emergence of a previously minor component of the original population.

Anemia and deficiencies of folate and vitamin B-6 are common and vary with season in Chinese women of childbearing age.

Little is known about the micronutrient status of Chinese women of childbearing age. We assessed nonfasting plasma concentrations of folic acid, vitamin B-12, vitamin B-6 (as pyridoxal-5'-phosphate), hemoglobin (Hb), ferritin and transferrin receptor (TfR) in 563 nonpregnant textile workers aged 21-34 y from Anqing, China. All women had obtained permission to become pregnant and were participating in a prospective study of pregnancy outcomes. Mean (SD) plasma concentrations were 9.7 (4.1) nmol/L folic acid, 367 (128) pmol/L vitamin B-12, 40.2 (15.8) nmol/L vitamin B-6, 108 (12. 9) g/L Hb, 42.6 (34.2) microgram/L ferritin and 5.2 (2.7) mg/L TfR. Twenty-three percent of women had biochemical evidence of folic acid deficiency, 26% were deficient in vitamin B-6 and 10% had low vitamin B-12. Overall, 44% of women were deficient in at least one B vitamin. Although anemia (Hb < 120 g/L) was detected in 80% of women, only 17% had depleted iron stores (ferritin < 12 microgram/L); 11% had elevated TfR concentrations. Distinct seasonal trends were observed in the prevalence of moderate anemia (Hb < 100 g/L) and deficiencies of folic acid and vitamin B-6, with significantly lower concentrations of folate and Hb occurring in summer and lower concentrations of vitamin B-6 occurring in winter and spring than in other seasons. We conclude that deficiencies of folic acid, vitamin B-6 and iron were relatively common in this sample of Chinese women of childbearing age and were contributing to the high prevalence of anemia. Without appropriate supplementation, these deficiencies could jeopardize the women's health and increase their risk of adverse pregnancy outcomes.

Treatment of poikiloderma of Civatte with an intense pulsed light source.

BACKGROUND: Effective treatment of poikiloderma of Civatte combines elimination of both the vascular and pigmented components simultaneously. A broad spectrum, noncoherent, intense pulsed light (IPL) source delivers multiple wavelengths with software controlled pulse durations and sequencing, which permits treatment of both vascular and pigmented lesions simultaneously. OBJECTIVE: To determine response and side effects of poikiloderma of Civatte of the neck and chest when treated by IPL. METHODS: One hundred and thirty-five patients randomly selected with typical changes of poikiloderma of Civatte on the neck and/or upper chest were treated with one to five treatments using IPL. RESULTS: Clearance of more than 75% of telangiectasias and hyperpigmentation comprising poikiloderma was observed. The incidence of side effects was 5%, including pigment changes. In many cases, improved skin texture was noted both by physician and patient. CONCLUSION: IPL is an effective mode of therapy for poikiloderma of Civatte. It offers a reduction of pigment and telangiectasias with a low risk profile. Additional benefits include subjective changes of improvement in skin texture.

Influence of the ventral hippocampal formation on plasma vasopressin, hypothalamic-pituitary-adrenal axis, and behavioral responses to novel acoustic stress.

The ventral hippocampal formation (vHF) seems to constrain diverse responses to psychological stimuli, and disruption of this function may underlie severe neuropsychiatric diseases. In particular, the ventral subiculum inhibits hypothalamic-pituitary-adrenal axis (HPA) activity following psychological, but not systemic, stressors. Despite the difficulty in interpreting such HPA responses, they have been relied upon to further characterize vHF function, because increased HPA axis activity is implicated in neuropsychiatric disturbances, and reliance on behavioral and cognitive data is even more problematic. Plasma arginine vasopressin (pAVP), which is inhibited by psychological stimuli and is also implicated in diverse neuropsychiatric diseases, provides a less ambiguous measure of CNS function. To test if its inhibition by psychological stress is also mediated by the vHF, we conducted two studies. In the first, pAVP and behavioral responses to novel acoustic stress were assessed in rats with bilateral excitotoxic lesions of the ventral subiculum and the ventral hippocampus. The subiculum lesions blocked the fall in pAVP and enhanced escape behaviors, whereas the hippocampal lesions produced responses intermediate to those in the subiculum-lesioned and control rats. In the second study, the pAVP response was similarly blocked by small lesions restricted to those vHF subfields which project to the neuroendocrine hypothalamus, compared to the response in animals with lesions in other vHF subfields. These results indicate that discrete projections from the vHF inhibit the pAVP response to psychological stimuli, and suggest that pAVP may provide a reliable probe of vHF activity.

A comparison of iron availability from commercial iron preparations using an in vitro digestion/Caco-2 cell culture model.

The objectives of this study were to compare iron availability from commercial preparations of FeSO(4), ferrous gluconate, ferrous fumarate, and a polysaccharide-iron complex using an in vitro digestion/Caco-2 cell culture model. In addition, we sought to determine if calcium carbonate and calcium acetate (common phosphate binding agents) inhibited iron availability from an oral iron supplement when digested simultaneously. Caco-2 cell ferritin formation following exposure to simulated gastric and intestinal digests of the iron supplements was used as a measure of iron uptake and availability. Plates without cell monolayers were included in each replication of the experiment to measure the total amount of soluble iron that resulted from the in vitro digestion. Significantly more iron was taken up from the FeSO(4), ferrous gluconate, and ferrous fumarate than the polysaccharide-iron complex. Similar results comparing FeSO(4) and the polysaccharide-iron complex have been observed in humans. In addition, less iron was taken up from digests with calcium carbonate relative to calcium acetate even though similar amounts of soluble iron were observed in these experiments. The results indicate that when iron supplements and phosphate binders are consumed simultaneously, calcium acetate may be the preferred phosphate binder to maximize iron availability.

Tumescent anesthesia in ambulatory phlebectomy: addition of epinephrine.

BACKGROUND: The advantages of using tumescent anesthesia for ambulatory phlebectomy have recently been described. Previously, tumescent solutions have avoided epinephrine for concerns of toxicity given the large volume of anesthetic sometimes used. OBJECTIVE: To evaluate the efficacy and safety of using epinephrine in the tumescent anesthesia solution during ambulatory phlebectomy. METHODS: Over the course of 1 year, epinephrine in the concentration of 1:100,000 was added to the tumescent solution of patients undergoing ambulatory phlebectomy. A retrospective review of 94 sequential patients was performed to determine the rate of complications associated with the procedure. RESULTS: The complication rate was considerably improved using tumescent lidocaine with epinephrine compared to a previously performed study of tumescent lidocaine without epinephrine. The rate of hematoma was decreased to nil while the rate of hyperpigmentation decreased from 3.6% to 0%. Overall, the rate of complications was improved when epinephrine was added to the tumescent lidocaine solution. Blood pressure measured every 5 minutes and heart rate measured continuously did not significantly change before, during or after infiltration of the anesthetic solution. CONCLUSIONS: Epinephrine in appropriate concentrations is clearly safe when used in the tumescent anesthetic solution during ambulatory phlebectomy and should be used to reduce the incidence of hematoma and hyperpigmentation.

Clozapine restores water balance in schizophrenic patients with polydipsia-hyponatremia syndrome.

Hyponatremia/hypoosmolemia causes marked morbidity and prolongs hospital stays in a significant subset of schizophrenic patients. Case reports with methodological limitations suggest clozapine ameliorates this water imbalance. To more conclusively assess this possibility, we completed a 24-week open-label study in 8 male polydipsic hypoosmolemic schizophrenic inpatients. Subjects were treated initially for 6 weeks with a conventional neuroleptic, which was replaced by 300, 600, and 900 (if tolerated) mg/day of clozapine for sequential 6-week periods. On clozapine, mean plasma osmolality rose an average of 15.2 mosm/kg (95% CI: 5.5-25.0). Dosage of 300 mg/day of clozapine was sufficient to normalize plasma osmolality and was generally well tolerated. Clozapine appears to be the first effective pharmacotherapy for severe water imbalance in schizophrenia.

Cancer mortality following treatment for adult hyperthyroidism. Cooperative Thyrotoxicosis Therapy Follow-up Study Group.

CONTEXT: High-dose iodine 131 is the treatment of choice in the United States for most adults with hyperthyroid disease. Although there is little evidence to link therapeutic (131)I to the development of cancer, its extensive medical use indicates the need for additional evaluation. OBJECTIVE: To evaluate cancer mortality among hyperthyroid patients, particularly after (131)I treatment. DESIGN: A retrospective cohort study. SETTING: Twenty-five clinics in the United States and 1 clinic in England. PATIENTS: A total of 35 593 hyperthyroid patients treated between 1946 and 1964 in the original Cooperative Thyrotoxicosis Therapy Follow-up Study; 91 % had Graves disease, 79% were female, and 65% were treated with (131)I. MAIN OUTCOME MEASURE: Standardized cancer mortality ratios (SMRs) after 3 treatment modalities for hyperthyroidism. RESULTS: Of the study cohort, 50.5% had died by the end of follow-up in December 1990. The total number of cancer deaths was close to that expected based on mortality rates in the general population (2950 vs 2857.6), but there was a small excess of mortality from cancers of the lung, breast, kidney, and thyroid, and a deficit of deaths from cancers of the uterus and the prostate gland. Patients with toxic nodular goiter had an SMR of 1.16 (95% confidence interval [CI], 1.03-1.30). More than 1 year after treatment, an increased risk of cancer mortality was seen among patients treated exclusively with antithyroid drugs (SMR, 1.31; 95% CI, 1.06-1.60). Radioactive iodine was not linked to total cancer deaths (SMR, 1.02; 95% CI, 0.98-1.07) or to any specific cancer with the exception of thyroid cancer (SMR, 3.94; 95% CI, 2.52-5.86). CONCLUSIONS: Neither hyperthyroidism nor (131)I treatment resulted in a significantly increased risk of total cancer mortality. While there was an elevated risk of thyroid cancer mortality following (131)I treatment, in absolute terms the excess number of deaths was small, and the underlying thyroid disease appeared to play a role. Overall, (131)I appears to be a safe therapy for hyperthyroidism.

Tumescent anesthesia in ambulatory phlebectomy.

BACKGROUND: Ambulatory phlebectomy is an elegant outpatient procedure for the removal of varicose veins. One of the keys to its success is the ability to perform the procedure under local anesthesia. A new form of anesthesia, tumescent anesthesia, has been developed for liposuction surgery and is now being expanded for use in other surgical disciplines. OBJECTIVE: To determine the efficacy and safety as well as review the use and advantages of tumescent anesthesia in ambulatory phlebectomy. METHODS: A retrospective review of phlebectomy cases performed in our offices under tumescent anesthesia. RESULTS: The reported level of intraoperative and postoperative pain was very low. The complication rate was consistent with other reports except for a higher number of hematomas (3.4%). CONCLUSIONS: Tumescent anesthesia provides a very safe, comfortable method of anesthetizing patients for ambulatory phlebectomy. Epinephrine, in appropriate concentrations, should be a part of all tumescent anesthetic solutions used for phlebectomy as it may decrease the incidence of hematoma.

Autologous donation error rates in Canada.

BACKGROUND: Although certain transfusion risks are eliminated by the use of autologous blood, clerical errors may still occur. In addition, because of differences in donor selection criteria and donor-patient expectations, the consequences of certain errors may be different in autologous and allogeneic donations. STUDY DESIGN AND METHODS: In January 1996, autologous donation error rates in Canada from 1989 to November 1995 were estimated by 1) a detailed questionnaire sent to hospitals supplied by the Canadian Red Cross, Blood Services, Transfusion Center of Quebec at Montreal autologous donation program (n = 31), 2) a review of that institution's quality assurance non-compliance reports, and 3) a detailed questionnaire sent to other Canadian Red Cross centers with autologous donation programs (n = 16) and hospital-based autologous programs in Canada (n = 3). The total number of autologous donations collected was determined from Canadian Red Cross annual reports and information supplied by hospital-based programs. RESULTS: There were 113 errors reported for 16,873 units collected by the Montreal center (1/149 units) based on collection center and hospital data. The most frequent errors were the late receipt of units for surgery (25% of errors) or the receipt of units in the wrong hospital (23%). Other Canadian programs reported 166 errors for approximately 53,500 units collected (1/322 units). However, this figure was based mainly on collection center, and not hospital, data. The most frequent errors were in labeling (48%) and component preparation (25%). One unit of autologous fresh-frozen plasma was transfused to the wrong recipient. Errors were more frequent if components were produced, if units were drawn in hospitals for interhospital transfer, or it units were shipped between Red Cross centers. CONCLUSION: Errors are not infrequent in autologous donation programs. Autologous transfusion should not be considered as being without risk.

Effect of anesthetic technique on cardiac morbidity following carotid artery surgery.

PURPOSE: To investigate the effect of anesthetic technique on cardiac morbidity after carotid artery surgery. PATIENTS AND METHODS: From 1991 to 1994, 266 consecutive carotid endarterectomies were performed under local/regional (n=140) or general anesthesia (n=126). The effects of anesthetic technique on postoperative adverse cardiac events were assessed retrospectively. RESULTS: Preoperative cardiac testing was performed in all patients undergoing general or local/regional anesthesia. Medical characteristics were similar among patients in both groups. Forty-seven adverse cardiac events (4 myocardial infarction, 9 congestive heart failure, 7 angina, and 27 new ventricular dysrhythmias) occurred postoperatively in 38 patients (14.3%). There were no deaths. The relative risks of general anesthesia for dysrhythmias, myocardial infarction, angina, congestive heart failure, and total adverse cardiac events were 2.22, 0.37, 0.83, 1.38, and 1.5, respectively. The only statistically significant differential was the increased risk of postoperative dysrhythmias after general anesthesia (P<0.03). CONCLUSIONS: Major cardiac morbidity following carotid endarterectomy is independent of anesthetic technique.

Prevention of OKT3 nephrotoxicity after kidney transplantation.

In our experience the use of OKT3 as prophylaxis in renal transplantation has been associated with an increased incidence of both delayed graft function and thromboses of graft vessels. OKT3 nephrotoxicity might have been favored by restriction of perioperative fluid infusion to prevent pulmonary edema and by the use of very high dose (30 mg/kg) of methylprednisolone (mPDS) before the first OKT3 injection to reduce the release of cytokines. This led us to modify our perioperative management in three ways: (1) hydration status was optimalized; (2) the calcium-channel blocker diltiazem, considered beneficial for recovery of graft function, was administered on the day of transplantation; and (3) the dose of mPDS given before the first OKT3 injection was fixed at 8 mg/kg. Comparison of two consecutive series of patients (group 1, control patients, N = 172; group 2, managed as described above, N = 173) showed that: (1) the incidence of delayed graft function fell from 52% in group 1 to 22% in group 2 (P < 0.0001): (2) the incidence of pulmonary edema was not significantly increased in group 2 (3.5% vs. 1.7% in group 1, P = 0.5); and (3) the frequency of intragraft thrombosis fell from 7.6% in group 1 to 1.2% in group 2 (P = 0.0034). Multivariate analysis showed that the volemia/diltiazem program and avoidance of high mPDS dose were the most important factors responsible for the reduced occurrence of delayed graft function and graft vessels thrombosis, respectively. We conclude that a combined strategy of appropriate dosage of steroids before the first OKT3 injection, administration of a calcium-channel blocker and optimalization of volemia is safe and efficiently prevents against OKT3 nephrotoxic effects.

Effects of naltrexone on mannerisms and water imbalance in polydipsic schizophrenics: a pilot study.

In an open design, the opiate antagonist, naltrexone (25 mg bid), was added for six weeks to the neuroleptic regimen of seven inpatient polydipsic hyponatremic schizophrenics. Mannerisms and diurnal weight change improved slightly, the latter probably not as a consequence of diminished intake alone. Further studies are needed to clarify if stereotypies and polydipsia are modulated by endogenous opiates, and if opiate antagonists are of therapeutic value in this population.