Anti-nociceptive and anti-inflammatory effects of some Jordanian medicinal plant extracts

An impaired host defense mechanism is well known in patients with liver cirrhosis (LC). Using a sinusoidal lavage method, lymphocytes were obtained from LC rats that were administered thioacetamide, and natural killer (NK) activity was measured by 51Cr-release assay. The NK cell count was measured by flow cytometric analysis using monoclonal antibody (Mab) 3.2.3 and/or CD 3-8+ as markers for NK cells, and by immunohistochemical staining using Mab 3.2.3. Furthermore, interferon (IFN) alpha was administered to LC rats and the subsequent changes in hepatic NK activity and NK cell count were observed. In the large granular lymphocyte (LGL)-rich fraction (Fr.1, LGLs: 60-90%), the NK activity was significantly lower in the LC rats (40.0 +/- 3.8%) compared to that in the control rats (48.4 +/- 4.3%) (P < 0.005). In addition, the number of NK cells in the liver tissues of the LC rats was significantly lower compared to that in the liver tissues of the control rats by morphometric analysis (P < 0.05). For LC rats, NK activity of the Fr.1 24 hr after IFN alpha administration (5 x 10(4) IU/100 g body weight) increased significantly (P < 0.005). Hepatic NK activity and NK cell count were reduced in the LC rats, and recovered following IFN alpha administration. The results obtained in this study may give clues to better understanding the impaired host defense mechanism in LC patients.     

Cryosurgical treatment of professional chronic radiodermatitis

The results of open cholecystectomy ([OC] n = 7) versus laparoscopic cholecystectomy ([LC] n = 7) in cirrhotic patients were analyzed prospectively. Groups were well matched for surgical indication, presence of ascites/bleeding tendency, and Child's grade. There was no mortality. Mean operating time was significantly longer in the LC group (155 +/- 47 vs. 103 +/- 25 min, p < 0.05). Operative blood loss was significantly greater in the OC group (128 +/- 125 vs. 642 +/- 467 ml, p < 0.05). No patient in LC group required blood transfusion in contrast to three patients in OC group. Compared with 0% postoperative complications in LC group, wound infections developed in 43% of the patients in OC group (p < 0.05). Mean hospital stay in LC group was significantly less (6.7 +/- 4 vs. 17.4 +/- 7.3 days, p < 0.01). Thus, contrary to previous belief, cirrhosis per se is not a contraindication to LC. Laparoscopic cholecystectomy may be the procedure of choice whenever cholecystectomy is indicated in a cirrhotic patient because it may be associated with less bleeding and fewer incision-related complications.     

Neuroendocrine changes in luteal function in patients with premenstrual syndrome

The present study evaluates the luteal progesterone (P) and LH secretions in 14 patients affected by premenstrual syndrome (PMS) and in 14 asymptomatic controls through the evaluation of their episodic release. PMS was prospectively confirmed in two consecutive menstrual cycles using Moos' Menstrual Distress Questionnaire. A pulsatility study was performed during the luteal phase. Blood samples were drawn every 10 min for 12 h, beginning at 0800 h. Statistically significant pulses were detected using the Detect program, and the degree of concordance of LH and P pulses was estimated. Similar mean 12-h P levels were found in controls (mean +/- SD, 13.9 +/- 9.3 nmol/L) and patients (14.2 +/- 10.1). LH levels were also similar in the two groups. Patients showed a higher P pulse frequency (13.4 +/- 1.8 vs. 11.4 +/- 2.3; P < 0.02) and a reduced amplitude of secretory episodes (126.5 +/- 61.6% vs. 187.1 +/- 126.7%; P < 0.03) than controls. Similarly, PMS patients showed pulsatile LH release of increased frequency and reduced amplitude than controls. A significant degree of concordance between LH and P pulses was observed in both groups, with a time lag of 0-10 min; that is, P secretory episodes follow LH with a delay of 0-10 min. These findings demonstrate that despite the fact that integrated P levels in PMS patients are similar to those in control subjects, the episodic secretion of the hormone is characterized by pulses of increased frequency and reduced amplitude. This phenomenon is temporally related to LH secretion, thus reinforcing the concept of PMS as a neuroendocrine disorder.     

Dependency on atrial electrophysiological properties of appearance of paroxysmal atrial fibrillation in patients with Wolff-Parkinson-White syndrome: evidence from atrial vulnerability before and after radiofrequency catheter ablation and surgical cryoablation

The pathogenesis of paroxysmal atrial fibrillation in patients with Wolff-Parkinson-White syndrome and the effects of elimination of accessory pathways on the appearance of atrial fibrillation are still controversial. Fifty-four patients with Wolff-Parkinson-White syndrome were classified into three groups: a No AF group (n = 24), patients without paroxysmal atrial fibrillation; an RF-AF Group (n = 12), patients with paroxysmal atrial fibrillation whose accessory pathways were eliminated using radiofrequency catheter ablation; and a Cryo-AF Group (n = 18), patients with paroxysmal atrial fibrillation whose accessory pathways were eliminated with surgical cryoablation. The electrophysiological characteristics of each group were evaluated prior to and following the elimination of their accessory pathways. As indices of atrial vulnerability, the presence of fragmented atrial activity and repetitive atrial firing zones were assessed. Inducibility of atrial fibrillation was significantly reduced following ablation of accessory pathways in the Cryo-AF group (83.3%-5.6%, P < 0.0001), while it was unchanged in the RF-AF group (83.3%-75%). In preablation studies, the effective refractory periods of the atrium in the RF-AF group and the Cryo-AF group were significantly shorter compared with the No AF group (204 +/- 18 ms, 197 +/- 16 ms vs 246 +/- 44 ms, respectively, P < 0.0001). Following ablation, the effective refractory period for patients in the Cryo-AF group was significantly prolonged compared with before ablation (197 +/- 16 ms to 232 +/- 24 ms, P < 0.0001). As a result of this prolongation of the effective refractory period of the atrium, the fragmented atrial activity and repetitive atrial response zones narrowed following ablation in the Cryo-AF group, but not in the RF-AF group. Therefore, the pathogenesis of atrial fibrillation in patients with Wolff-Parkinson-White syndrome may depend on the refractory period of the atrium rather than on the presence of accessory pathways.     

Antihypertensive effects of combined lisinopril and hydrochlorothiazide in elderly patients with systodiastolic or systolic hypertension: results of a multicenter trial

This study was aimed at evaluating the antihypertensive effect of lisinopril and hydrochlorothiazide administered in the fixed combination of 20 and 12.5 mg, respectively, on clinic and 24-h blood pressure in elderly patients (age, 68.8 +/- 5.8 years, mean +/- SD) with mild-to-moderate essential systodiastolic or isolated systolic hypertension. After a washout period of 4 weeks, patients received once daily lisinopril combined with hydrochlorothiazide for a 6-week period. At the end of the washout and treatment periods, clinic blood pressure was assessed 24 h after dosing, and 24-h ambulatory blood pressure was monitored, taking blood pressure readings every 15 min. Pretreatment clinic blood pressure was 171.3 +/- 14.0/103.7 +/- 5.1 mm Hg (systolic/diastolic) in the group with systodiastolic hypertension (n = 405) and 179.6 +/- 9.4/83.6 +/- 5.4 mm Hg in the group with isolated systolic hypertension (n = 165). The corresponding 24-h average blood pressures were 144.1 +/- 13.9/88.7 +/- 8.4 mm Hg (n = 114) and 150.7 +/- 15.5/80.8 +/- 9.4 mm Hg (n = 40). Clinic blood pressure was significantly reduced by treatment in both groups. This was the case also for ambulatory blood pressure, which was reduced by 9.6 +/- 0.9%/9.9 +/- 0.9% in systodiastolic and by 11.8 +/- 1.3%/8.5 +/- 1.5% in isolated patients with systolic hypertension (p < 0.05 at least for all differences). The antihypertensive effect was similar in patients older and younger than 70 years. In all groups, it was manifest both during the day and the nighttime and was still significant after 24 h. Thus single daily administration of combined lisinopril-hydrochlorothiazide effectively reduces blood pressure in elderly patients with hypertension.     

Morning hypercoagulability and hypofibrinolysis. Diurnal variations in circulating activated factor VII, prothrombin fragment F1+2, and plasmin-plasmin inhibitor complex

The role of percutaneous needle aspiration for therapy of uncomplicated, large amoebic liver abscess (ALA) is not defined. Twenty nine patients of ALA with a cavity larger than 5 cm were randomised to two groups: (i) metronidazole 800 mg tid for 10 days combined with needle aspiration (group A, n = 15) and (ii) metronidazole therapy alone (group B, n = 14). Clinical parameters, viz, fever, pain and abdominal tenderness were recorded daily and graded 0 to 3 (in order of increasing severity). A statistically significant benefit was demonstrated in group A for clinical parameters evaluated. Group A patients took less time to become afebrile from the grade 2 level as compared to group B (3.8 +/- 1.7 days and 5.6 +/- 2.2 days respectively; p < 0.05). Reduction in pain intensity and abdominal tenderness from grade 2 to 1 also occurred earlier in group A (0.7 +/- 0.7 days vs 2.9 +/- 0.9 days for pain, P < 0.001 and 1.7 +/- 0.8 days vs 2.9 +/- 1.2 days for abdominal tenderness, p < 0.001). The mean duration of hospitalization was significantly shorter in group A as compared to group B (5.8 +/- 0.8 days vs 7.4 +/- 1.5 days, p < 0.001). Improvement in haematological and biochemical variables was similar in both groups. We conclude that percutaneous therapeutic needle aspiration of uncomplicated, large ALA hastens clinical recovery.     

The menstrual cycle and its effect on inflammatory bowel disease and irritable bowel syndrome: a prevalence study

OBJECTIVE: Female patients with bowel disease commonly report worsening symptoms in relation to the menstrual cycle. Our aim was to determine the nature of gastrointestinal symptoms correlating with the menstrual cycle in women with inflammatory and irritable bowel disease. METHODS: This was a retrospective study involving 49 women with ulcerative colitis (UC), 49 women with Crohn's disease (CD), 46 women with irritable bowel syndrome (IBS), and 90 healthy community controls. Participants were interviewed using a questionnaire including information regarding general health, medication history, pregnancy, as well as premenstrual and menstrual symptoms. Chi2 testing and logistic regression modeling were used to test for differences in frequencies between groups and for risk analysis. RESULTS: Premenstrual symptoms were reported by 93% of all women but statistically more often by patients with CD (p < 0.01). CD patients were also more likely to report increased gastrointestinal symptoms during menstruation ( < 0.01), diarrhea being the symptom reported most often. All disease groups had a cyclical pattern to their bowel habits significantly more than controls (p=0.01). Cyclical symptoms included diarrhea, abdominal pain, and constipation. Logistic regression revealed an odds ratio (OR) of 1.1 (95% CI 0.9-1.2) for experiencing bowel symptoms during the premenstrual and menstrual phases and an OR of 2.0 (95% CI 1.2-3.2) for experiencing a cyclical pattern in bowel habit changes in women with bowel disease. CONCLUSION: The prevalence of menstrually related symptoms is high, and appears to affect bowel patterns. The physiological and clinical effects of the menstrual cycle should be taken into consideration when assessing for disease activity.     

Gallbladder dyskinesia in acalculous biliary colic

AIMS: To test the hypotheses that: 1) postprandial gallbladder emptying might be abnormal in patients with acalculous biliary colic; and 2) that hymecromone, a drug that increases bile flow and relaxes biliary muscle might improve symptoms. METHODS: Twenty-four women were studied. Twelve patients presented recurrent biliary type of pain in the absence of gallstones, and persistence of contrast in the gallbladder, 24 hours after an oral cholecystogram, suggesting cholesterolosis. Twelve healthy volunteers used as controls had no symptoms and the gallbladder was not visible the day after an oral cholecystogram. Gallbladder emptying induced by an oral meal was studied with ultrasound in both groups before and after the administration of hymecromone. RESULTS: Gallbladder volumes were similar in both groups (23 +/- 10 ml vs. 31 +/- 11 ml; NS). Gallbladder emptying in the control group was simple exponential (R2 = 0.948 +/- 0.059) with a rate of 32 +/- 16 minutes. Gallbladder emptying was bimodal in patients. Gallbladder volume increased to 120% in the first 10 minutes, to empty exponentially thereafter (R2 = 0.964 +/- 0.040. Rate: 29 +/- 22 minutes). This resulted in a marked reduction in gallbladder volume emptied at 40 minutes when compared to controls (30% +/- 27% vs. 54% +/- 14%; p = 0.012). Pretreatment of controls with hymecromone induced an emptying pattern similar to that of patients. In patients, emptying after hymecromone did not change but symptoms were improved. CONCLUSIONS: An abnormal emptying pattern of the gallbladder was identified in patients with acalculous biliary colic, and hymecromone was partly effective to reduce pain, despite a minor effect on gallbladder emptying pattern.     

Fibromyalgia in hepatitis C virus infection. Another infectious disease relationship

BACKGROUND: Fibromyalgia syndrome (FS) is a common disorder of diffuse pain in the muscles or joints accompanied by tenderness at specific tender points and a constellation of related symptoms. The potential role of infections in the pathogenesis of FS has only recently been investigated. OBJECTIVES: To evaluate the prevalence of FS and to assess tenderness thresholds in patients infected with hepatitis C virus (HCV). METHODS: The study included 90 patients with HCV, 128 healthy, anti-HCV-negative controls, and 32 patients with non-HCV-related cirrhosis. Tenderness was measured by manual palpation (18 tender points) and with a dolorimeter. Fibromyalgia syndrome was diagnosed according to the 1990 American College of Rheumatology criteria. RESULTS: The diagnosis of FS was established in 14 patients (16%) with HCV, in 1 patient (3%) with non-HCV-related cirrhosis, and in none of the healthy controls (P < .001). Thirteen of the HCV-positive patients with FS were women. The patients with HCV had significantly (P < .01) more tender points (mean [+/- SD] 3.6 +/- 5.3) than the healthy controls (0.1 +/- 0.5) and the patients with non-HCV-related cirrhosis (1.2 +/- 2.7). Specifically, the patients with cirrhosis were most tender on both tenderness measures owing to the high proportion of women in this group. Patients with FS were significantly more tender than those without FS: their dolorimetry thresholds were 2.9 kg vs 6.0 kg (P < .001). CONCLUSIONS: A high prevalence of FS was observed in patients infected with HCV, especially women. Recognizing FS in patients with HCV will prevent misinterpretation of FS symptoms as part of the liver disease and will enable the physician to reassure the patient about these symptoms and to alleviate them.     

A prospective assessment of gastroesophageal reflux before and after treatment of achalasia patients: pneumatic dilation versus transthoracic limited myotomy

OBJECTIVES: We conducted this study to determine whether reflux should be a major consideration in the choice of treatment for achalasia patients. Achalasia patients undergoing either pneumatic dilation or transthoracic limited esophagomyotomy were monitored for reflux before and after treatment, for comparison. METHODS: Twenty-four hour ambulatory esophageal pH tests and esophageal manometry were performed on 32 consecutive, untreated achalasia patients. Studied (before and after treatment) were 17 patients who underwent pneumatic dilation and 15 patients who received transthoracic limited myotomy without fundoplication. All follow-up studies were completed within 12 months of treatment. RESULTS: The ages of the two groups were not significantly different (p > 0.05, 45 +/- 9 yr myotomy vs. 44 +/- 13 yr dilation). The resting lower esophageal sphincter pressure was not significantly different (p > 0.05 before treatment) between groups but was reduced significantly (p < 0.05 after treatment) in both groups (30 +/- 9 mm Hg before vs. 9 +/- 4 mm Hg after myotomy, and 27 +/- 10 mm Hg before vs. 11 +/- 4 mm Hg after pneumatic dilation. The total time the pH was < 4.0 was not significantly different, p > 0.05, in either group before treatment (myotomy, 3.7 +/- 4.4%; dilation, 2.9 +/- 4.9%) or after treatment (myotomy, 8.6 +/- 9.2%; dilation, 10.2 +/- 15.9%). Twelve of 32 patients (38%), had a percent total time < 4.0 that exceeded 6% after treatment, eight of whom were asymptomatic. CONCLUSIONS: These results indicate that the amount of reflux after treatment by both pneumatic dilation and transthoracic esophagomyotomy is similar. The absence of reflux symptoms in treated achalasia patients does not exclude the possibility of significant acid reflux.     

Prospective outcome evaluation of spinal cord stimulation in patients with intractable leg pain

STUDY DESIGN: The results of spinal cord stimulation were prospectively evaluated using both subjective patient self-report measures and objective physical functional testing. OBJECTIVES: The purpose of this study was to evaluate prospectively the effects of spinal cord stimulation implantation, performed with the patient awake and providing feedback, in patients with primary reports of intractable leg pain. SUMMARY OF BACKGROUND DATA: Spinal cord stimulation has been used for treating chronic pain of many types. However, even among those with intractable lower extremity pain, the outcome results have shown great variability. METHODS: The surgical procedure was performed with the patient awake and providing feedback to ensure optimal pain relief from the lead placement. The study group comprised 40 patients, ranging in age from 28 to 86 years. The average symptom duration was 65.4 months, and the average number of prior lumbar spine surgeries was 2.3 (range, 1 to 8). The primary data collection periods were preoperative, 6 weeks after, and 12 and 24 months after surgery. RESULTS: Statistically significant improvement in isometric lower extremity function was demonstrated 6 weeks after the spinal cord stimulation implantation. In the more painful leg, the performance increased from 457.5 ft-lb-sec to 629.8 ft-lb-sec (P < 0.01). The performance remained significantly improved at the 12- and 24-month follow-ups. Significant improvement was demonstrated on the physical scale of the Sickness Impact Profile at 6 weeks. At 24 months, all three scales (physical, psychological, and other) as well as the total score were significantly improved. Statistically significant decreases in pain, assessed by changes in visual analog scale scores, were noted in the legs, when walking, and in overall lifestyle. The use of narcotic medication decreased at all follow-up periods. At least 66% of the patients who were taking narcotics before spinal cord stimulation were taking reduced amounts or no narcotics 2 years later. At the time of the 24-month follow-up, at least 70% of patients reported that the procedure helped them, and would recommend it to someone with similar symptoms. CONCLUSIONS: Spinal cord stimulation implantation can result in improved physical function and decreased pain in patients who are carefully screened and in whom the implantation is performed with the patient awake to help ensure optimal pain-relieving lead placement.     

Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia

OBJECTIVE: Although opioid analgesics are used in the management of neuropathic pain syndromes, evidence of their efficacy remains to be established. We evaluated the clinical efficacy and safety of oxycodone in neuropathic pain using postherpetic neuralgia as a model. METHODS: Patients with postherpetic neuralgia of at least moderate intensity were randomized to controlled-release oxycodone 10 mg or placebo every 12 hours, each for 4 weeks, using a double-blind, crossover design. The dose was increased weekly up to a possible maximum of 30 mg every 12 hours. Pain intensity and pain relief were assessed daily, and steady (ongoing) pain, brief (paroxysmal) pain, skin pain (allodynia), and pain relief were recorded at weekly visits. Clinical effectiveness, disability, and treatment preference were also assessed. RESULTS: Fifty patients were enrolled and 38 completed the study (16 men, 22 women, age 70+/-11 years, onset of postherpetic neuralgia 31+/-29 months, duration of pain 18+/-5 hours per day). The oxycodone dose during the final week was 45+/-17 mg per day. Compared with placebo, oxycodone resulted in pain relief (2.9+/-1.2 versus 1.8+/-1.1, p=0.0001) and reductions in steady pain (34+/-26 versus 55+/-27 mm, p=0.0001), allodynia (32+/-26 versus 50+/-30 mm, p=0.0004), and paroxysmal spontaneous pain (22+/-24 versus 42+/-32 mm, p=0.0001). Global effectiveness, disability, and masked patient preference all showed superior scores with oxycodone relative to placebo (1.8+/-1.1 versus 0.7+/-1.0, p=0.0001; 0.3+/-0.8 versus 0.7+/-1.0, p=0.041; 67% versus 11%, p=0.001, respectively). CONCLUSIONS: Controlled-release oxycodone is an effective analgesic for the management of steady pain, paroxysmal spontaneous pain, and allodynia, which frequently characterize postherpetic neuralgia.     

Urinary excretion of arsenic species after exposure to arsenic present in drinking water

The effects of intravenous MS-551, a new class III antiarrhythmic drug, on atrium and ventricle were evaluated in 6 patients with ventricular tachyarrhythmias (4 males and 2 females; mean age 45 +/- 21 years) in an electrophysiologic study. Two patients had sustained ventricular tachycardia (VT) and 4 patients had ventricular fibrillation (VF). Electrophysiologic study was performed before and after the administration of MS-551 (loading infusion 0.3 mg/kg for 5 min + 0.01 mg/kg/min). The QT and QTc intervals were significantly prolonged by MS-551 from 359 +/- 52 to 411 +/- 63 msec (p = 0.01) and from 410 +/- 36 to 452 +/- 47 (p = 0.0172), respectively. No effect was observed on the sinus cycle length, QRS duration, or AH and HV intervals in sinus rhythm. The effective refractory periods of the right atrium (AERP) were significantly prolonged at paced cycle lengths of 600 (from 222 +/- 19 to 250 +/- 23 msec, p = 0.0009), 400 (from 207 +/- 15 to 228 +/- 15, p < 0.0001) and 300 (from 193 +/- 10 to 205 +/- 8 msec, p = 0.0127) msec. Similarly, the right ventricular ERP (VERP) were significantly prolonged at paced cycle lengths of 600 (from 240 +/- 23 to 268 +/- 23 msec, p < 0.0001), 400 (from 225 +/- 22 to 250 +/- 24 msec, p = 0.0007), and 300 msec (from 213 +/- 14 to 228 +/- 18 msec, p = 0.0071). MS-551 prolonged AERP and VERP in a "reverse" use-dependent manner without changing the conduction time in patients with ventricular tachyarrhythmias. MS-551 prevented the induction of VT in 1 patient and VF in only 1 patient in this electrophysiologic study. Further evaluation of the therapeutic potential of MS-551 using higher dosages is necessary.     

Intrasphincteric injection of botulinum toxin is effective in long-term treatment of esophageal achalasia

We investigated the long-term efficacy and safety of intrasphincteric injections of botulinum toxin (100 U) in 57 patients with esophageal achalasia. One month after treatment, 50 patients had improved (88%); both symptom score and LES pressure were significantly reduced (P < 0.001). After a mean follow-up of 24+/-15 months (range 6-48), 43 patients (75%) are still in remission, although repeat injections of toxin were needed to achieve a stable effect on symptoms.     

A single dose of morphine sulfate increases the incidence of vomiting after outpatient inguinal surgery in children

BACKGROUND: In children, opioids are valuable both for their analgesic properties and for their salutary effect on emergence delirium. Although intraoperative administration of opioids is often cited as the cause of postoperative emesis, few data quantitating the magnitude of this effect exist. METHODS: Patients undergoing inguinal surgery as outpatients were randomly assigned to one of two groups. One group received a single intravenous dose of morphine 0.1 mg/kg (morphine group), and the other (control) group had the identical anesthetic but instead received saline. Intravenous ketorolac was administered in response to verbal complaints of pain or a Children's Hospital of Eastern Ontario Pain Score greater than 9 on two successive evaluations performed at 5-min intervals. The authors compared the incidence of postoperative emesis and emergence, behavior, and pain scores between the two groups. RESULTS: Patients in the morphine group (n = 48) were 5.6 +/- 2.8 yr old and weighed 20.8 +/- 7.8 kg, and those in the control group (n = 49) were 4.5 +/- 2.9 yr old and weighed 18.9 +/- 9.2 kg. More patients in the morphine group were cooperative and deeply asleep both on arrival and through the first 30 min of their stay in the postanesthesia care unit (PACU) (P < 0.05). Sixty-three percent of the children in the control group received ketorolac in the PACU compared with 20% of the morphine group (P < 0.01). The incidence of emesis for the 24 h after arrival in the PACU was 56% for those who received morphine compared with 25% in the control group (P < 0.01). CONCLUSIONS: For children undergoing inguinal surgery, the administration of a single dose of intravenous morphine after the induction of anesthesia smooths emergence from anesthesia as assessed by improved cooperation and sedation in the PACU, decreases the need for postoperative analgesics, but increases the incidence of vomiting in the first 24 h after surgery.     

Quantitation of three-month intraindividual variability and influence of sex and menstrual cycle phase on CYP1A2, N-acetyltransferase-2, and xanthine oxidase activity determined with caffeine phenotyping

OBJECTIVE: To evaluate intraindividual variability and the effects of sex and menstrual cycle phase on the activity of cytochrome P450 1A2 (CYP1A2), N-acetyltransferase 2 (NAT2), and xanthine oxidase. METHODS: Ten white men were given 2 mg/kg caffeine orally every 14 days for 3 months. The same dosage of caffeine was given to 10 premenopausal white women during the midfollicular and midluteal phases of three complete menstrual cycles. Phenotype was determined with urinary caffeine metabolite ratios. RESULTS: For CYP1A2, mean metabolic ratio (+/- SD) was 5.97 +/- 2.78 during the midfollicular phase and 5.32 +/- 1.99 during the midluteal phase (p = 0.2). For extensive and poor metabolizer of NAT2. Mean midfollicular phase metabolite ratios were 0.71 +/- 0.060 and 0.37 +/- 0.030, and mean midluteal phase metabolite ratios were 0.69 +/- 0.076 and 0.39 +/- 0.053 (p = 0.9). For xanthine oxidase, mean midfollicular phase metabolite ratio was 0.63 +/- 0.06 and mean midluteal phase metabolite ratio was 0.63 +/- 0.05 (p = 0.3). Among the men, mean CYP1A2, NAT2 rapid and slow acetylator, and xanthine oxidase indices were 9.42 +/- 10.18, 0.66 +/- 0.021, 0.31 +/- 0.056, and 0.64 +/- 0.03. There were no differences in metabolite ratios between men and women for CYP1A2, NAT2 extensive metabolizers, or xanthine oxidase. A statistically significant sex difference was found for poor metabolizers of NAT2 (p < 0.05). Median coefficients of variation for CYP1A2, NAT2 extensive and poor metabolizers, and xanthine oxidase ratios were 16.8% (range, 4.5% to 49.3%), 2.9% (range, 2.2% to 4.7%), 13.4% (range, 7.5% to 27.2%), and 4.5% (range, 2.3% to 13.0%). CONCLUSION: Stratification by menstrual cycle phase or sex need not be performed for pharmacokinetic or clinical investigations of substrates for CYP1A2, NAT2, or xanthine oxidase in which the subject are adults.     

Magnesium supplementation alleviates premenstrual symptoms of fluid retention

We investigated the effect of a daily supplement of 200 mg of magnesium (as MgO) for two menstrual cycles on the severity of premenstrual symptoms in a randomized, double-blind, placebo-controlled, crossover study. A daily supplement of 200 mg of Mg (as MgO) or placebo was administered for two menstrual cycles to each volunteer, who kept a daily record of her symptoms, using a 4-point scale in a menstrual diary of 22 items. Symptoms were grouped into six categories: PMS-A (anxiety), PMS-C (craving), PMS-D (depression), PMS-H (hydration), PMS-O (other), and PMS-T (total overall symptoms). Urinary Mg output/24 hours was estimated from spot samples using the Mg/creatinine ratio. Analysis of variance for 38 women showed no effect of Mg supplementation compared with placebo in any category in the first month of supplementation. In the second month there was a greater reduction (p = 0.009) of symptoms of PMS-H (weight gain, swelling of extremities, breast tenderness, abdominal bloating) with Mg supplementation compared with placebo. Compliance to supplementation was confirmed by the greater mean estimated 24-hour urinary output of Mg (p = 0.013) during Mg supplementation (100.8 mg) compared with placebo (74.1 mg). A daily supplement of 200 mg of Mg (as MgO) reduced mild premenstrual symptoms of fluid retention in the second cycle of administration.     

Prognostic value of Doppler transmitral flow velocity patterns in acute myocardial infarction

Doppler transmitral flow patterns are partially dependent on age. We investigated the correlations between the age-adjusted transmitral flow patterns, hemodynamic indexes, and the coronary and clinical outcome in 206 patients with acute myocardial infarction (AMI) and 102 normal control subjects. The peak flow velocity at atrial contraction was significantly lower in 50 of the 206 patients (24%) (low-A group) than in the 102 normal controls. Pulmonary capillary wedge pressure was significantly higher in the low-A group than in the remaining 156 patients with AMI (20 +/- 7 vs 11 +/- 5 mm Hg, p <0.001), and the cardiac index and left ventricular ejection fraction were significantly lower (2.2 +/- 0.6 vs 2.9 +/- 0.7 L/min/m2, p <0.001; 38 +/- 15% vs 52 +/- 13%, p <0.001). The incidence of cardiogenic shock was significantly higher in the low-A group than in the other patients with AMI (42% vs 19%, p <0.001). Regression analysis demonstrated a significant association between decreased atrial filling velocity and increased in-hospital mortality as well as the incidence of heart failure in AMI (p <0.001). The 5-year mortality rate was also significantly higher in the low-A group (p <0.001). The age-adjusted transmitral flow pattern in AMI can identify patients with left ventricular dysfunction, which can lead to a poor prognosis.     

Abnormal gastro-oesophageal reflux in Chinese with atypical chest pain

Although atypical chest pain has been well described in the Western population, its frequency in Chinese is unknown. Over a period of 42 months, we studied 521 Chinese patients with chest pain and identified 108 patients (20.7%) whose pain was not related to cardiac causes, as determined by exercise ECG or cardiac catheterization. Using 24 h ambulatory pH monitoring and baseline oesophageal manometry, 28.7, 19.4 and 5.6% of these patients were found to have abnormal reflux parameters, abnormal manometric findings or both, respectively. There were significantly more patients complaining of chest pain during the study in the gastro-oesophageal reflux disease (GERD) group than in the non-GERD group (16/31 vs 20/77; P < 0.001). The lower oesophageal sphincter pressure was lower in those with abnormal reflex parameters than in those with normal reflux parameters (12.7 +/- 5.4 vs 17.8 +/- 5.8 mmHg; P < 0.05). There was no significant difference in symptoms, such as heartburn (54.8 vs 42.9%), regurgitation (38.7 vs 35.1%) and dysphagia (19.4 vs 24.7%), among the two groups. Non-specific changes were the most frequent baseline motility pattern. In conclusion, atypical chest pain and gastro-oesophageal reflux disease are not uncommon in Chinese and this deserves special emphasis as the continuation of anti-anginal drugs may aggravate their condition.     

Evaluation of proteolytic activity of micro-organisms isolated from dry cured ham

BACKGROUND: Morphologic changes of the vascular endothelium are common in patients with systemic sclerosis and Raynaud's phenomenon. The aim of this study was to evaluate the endothelium-dependent vasodilatation and endothelium-independent vasodilatation and to examine the effects of short-term estrogen administration on vascular responses in these patients. METHODS AND RESULTS: The study included 12 female patients with systemic sclerosis and Raynaud's phenomenon (aged 49+/-14 years) and 12 age- and sex-matched healthy control subjects. With the use of high-resolution ultrasound imaging, brachial artery diameter was measured at rest, during reactive hyperemia (endothelium-dependent response), and after administration of sublingual nitroglycerin (endothelium-independent dilatation). Intima-media thickness of the common carotid artery was also measured. Baseline diameter was similar in patients and control subjects; intima-media thickness was significantly higher in patients (0.83+/-0.3 vs 0.46+/-0.2 mm, P= .002) than in control subjects. Flow-mediated dilatation was reduced in patients (3.6%+/-7% vs 11.9%+/- 4.6%, P = .003); endothelium-independent dilatation also was reduced in patients with Raynaud's phenomenon (14%+/-7% vs 23%+/-6%, P= .003). Vascular responses in 10 patients were examined 15 minutes after administration of conjugated estrogens (25 mg intravenously); there was a significant increase of endothelium-dependent dilatation after estrogen administration (1.7%+/-4% to 6.3%+/-4%, P= .01), whereas endothelium-independent dilatation did not change (13.4%+/-8% to 15.5%+/-7%, not significant). CONCLUSIONS: Endothelium-dependent vasodilatation and endothelium-independent vasodilatation are impaired in patients with Raynaud's phenomenon secondary to systemic sclerosis, whereas intima-media thickness is increased. Short-term estrogen administration can improve endothelial dysfunction in this group of patients.