Bacillus Calmette-Guerin Immunotherapy for Recurrent Multiple Warts: An Open-Label Uncontrolled Study.

BACKGROUND: Cutaneous warts present a therapeutic challenge because of recurrence and multiplicity and may become a frustrating condition for both patients and physicians. In the past few years, there has been an increase in intralesional immunotherapy for recurrent multiple warts not only because of its encouraging results in the treatment but also due to its ability to clear distant warts and preventing recurrence. OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of intralesional bacillus Calmette-Guerin (BCG) vaccine immunotherapy in the treatment of recurrent multiple warts. MATERIALS AND METHODS: This study included 40 adult patients with multiple recurrent extragenital warts of different sizes, numbers, and duration, with or without distant warts. Patients were injected intralesionally with 0.1 ml BCG vaccine into the largest wart at a 3-week interval, directly without a pre-sensitization skin test, until complete clearance or for a maximum of three sessions. Follow-up was done every month for 3 months to detect any recurrence. RESULTS: Out of the 40 patients enrolled in the study, 34 patients completed the treatment protocol of three injections and 3 months of follow-up and six patients discontinued for various reasons. Complete clearance of the lesions was achieved in 25 (73.53%) patients, partial clearance in 8 (23.53%) patients, and no response in 1 (2.94%) patient. Complete response was demonstrated in 75% of those presenting with distant warts. Therapy-related side effects were mild in the form of pain during injection, itching, erythema at the site of injection, and flu-like symptoms. None of the patients with complete response showed recurrence of lesions in a 3-month follow-up period. CONCLUSION: Intralesional BCG immunotherapy is a safe, effective, and promising treatment modality for recurrent multiple warts.

Pattern of chilblains in a high altitude region of Ladakh, India.

BACKGROUND: Extreme sub-zero temperature in winters (15 °C to -25 °C), high velocity winds and wind-chill factor pose risk to those who resides at the high altitude environment to develop cold related injuries like chilblains and frostbite. The aim of this study was to study the patterns of chilblains in high altitude region like Ladakh. METHODS: The study was conducted at Dermatology outpatient department of Military Hospital, Leh from 1 Sep 2009 to 31 May 2010. Patients, satisfying clinical criteria for the diagnosis of chilblains were included into the study. Detailed history and thorough clinical examination was conducted. Complete blood count and Urine routine examination was carried out in every patient. Anti Nuclear Factor tests were carried out in only those who had history suggestive of connective tissue disease. RESULTS: Total 108 (5.75%) were diagnosed to have chilblains. Only a single case of chilblain was found in a local resident (p < 0.005). Family history of chilblains was present in 10 (9.2%) patients, there was recurrence in 12 (11.1%) and 21 patients (19.4%) were smokers. Most (63.8%) of the patients, had BMI between 20 and 22 kg/m(2) (mean = 20.03 kg/m(2); 95% CI = 19.68-20.38 and SD 1.82). 42.1% of cases of chilblains also had hyperhidrosis (p < 0.05). CONCLUSION: In a HA area like Ladakh, the non-natives suffer maximum from chilblains. This could be explained by the protective genetic adaptability of natives to extreme cold environment and their protective life style against cold. Low body mass index (BMI) and hyperhidrosis are important associations for development of chilblains.

Acanthosis nigricans associated with transitional cell carcinoma of the urinary bladder.

An elderly man from the region of Ladakh presented with recurrent episodes of lower respiratory tract infection, rapidly progressive Acanthosis nigricans, Acanthosis palmaris and plantar keratoderma. Detailed investigations revealed underlying metastatic transitional cell carcinoma of the bladder. This case is being reported for its rarity in the literature.

Pregnancy augments nitric oxide-dependent dilator response to acetylcholine in the human uterine artery.

The influence of pregnancy on the dilator effects of acetylcholine in the isolated human uterine artery was investigated. Acetylcholine (0.1 nM to 0.1 microM) produced concentration- and endothelium-dependent relaxation of norepinephrine (3 microM)-induced contraction. The relaxation was greater in arteries from pregnant patients (P arteries) than from non-pregnant patients (NP arteries). The maximal relaxation was 53.5+/-3.4% (n=21) in P arteries and 23.5+/-2.5% (n=35) in NP arteries. In both P and NP arteries the cholinergic relaxation was increased in the presence of superoxide dismutase and greatly reduced in the presence of the nitric oxide synthase inhibitors, NG-mono-methyl L-arginine (L-NMMA) and L-nitro-arginine-methylester (L-NAME). The effect of these nitric oxide synthase inhibitors was reversed by L-arginine. We conclude that pregnancy enhances acetylcholine-induced nitric oxide synthesis and release in the human uterine artery.

Stimulation of alpha 2 adrenoceptors dilates the rat middle cerebral artery.

BACKGROUND: Because alpha 2 adrenoceptor agonists are used as adjuncts to anesthetics, their effects on the cerebrovascular circulation are of prime importance. We studied changes in the diameter of rat middle cerebral arteries after stimulation of alpha 2 adrenoceptors with UK14,304. METHODS: Rat middle cerebral arteries were isolated, cannulated at each end with a glass micropipette, and pressurized to 85 mmHg. The middle cerebral arteries were immersed in a bath (37 degrees C) containing physiologic saline solution, and luminally perfused with physiologic saline solution (100 microliters/ min). Changes in vessel diameter were measured after magnification with a microscope. RESULTS: Resting diameter of the middle cerebral arteries was 239 +/- 13 microns (n = 8) for the first study. A dose-dependent dilation was produced by addition of UK14,304 to the extraluminal bath; a 10-15% increase in diameter occurred at a concentration of 10(-4)M. The dilations produced by UK14,304 were blocked with selective alpha 2-antagonists, idazoxan and rauwolscine, but not by the selective alpha 1-antagonist, prazosin. The dilations could be blocked by removal of the endothelium, or the nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (10(-5) M). The inhibitory effects of N-nitro-L-arginine methyl ester were reversed with the addition of 10(-3) M L-arginine, but not 10(-3) M D-arginine. Furthermore the dilation produced by UK14,304 was completely abolished with pertussis toxin (100 ng/ml). CONCLUSIONS: It was concluded that the stimulation of alpha 2 adrenoceptors with UK14,304 produced a dilation in the rat middle cerebral artery that (1) was dependent on intact endothelium, (2) involved nitric oxide, and (3) acted via a pertussis toxin-sensitive G protein.

Permissive role of NO in alpha 2-adrenoceptor-mediated dilations in rat cerebral arteries.

Dilations produced with UK-14304, a selective alpha 2-adrenoceptor agonist, in rat middle cerebral arteries (MCAs) were blocked after removal of the endothelium or inhibition of nitric oxide synthase (NOS). After endothelium removal or inhibition of NOS, the addition of subthreshold doses of an exogenous nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine, restored the dilations produced by UK-14304. In a similar manner the guanosine 3',5'-cyclic monophosphate (cGMP) analogues 8-bromoguanosine 3',5'-cyclic monophosphate and N2,2'-O-dibutyrylguanosine 3',5'-cyclic monophosphate restored the dilations of MCAs after endothelial removal. Because NO cannot be synthesized and released in MCAs after inhibition of NOS, it cannot be directly responsible for the dilation. The basal release of NO from the endothelium acts permissively in the vasodilation by maintaining adequate levels of cGMP. Removal of this basal release of NO by removal of endothelium or inhibition of NOS abolishes the alpha 2-adrenoceptor-mediated dilation.

Pregnancy-induced alterations of neurogenic constriction and dilation of human uterine artery.

The responses to electrical field stimulation (EFS) of perivascular nerves in human uterine arteries were characterized. The arteries were removed from pregnant and nonpregnant patients undergoing hysterectomy. Tetrodotoxin, guanethidine, and phentolamine blocked EFS (2 min, 80 V, 0.1-ms duration)-induced constriction. The constrictions and the endogenous norepinephrine levels were lower (P < 0.01) in uterine arteries from pregnant than from nonpregnant patients. When arterial rings were precontracted, the response to EFS was biphasic, consisting of an initial constriction followed by a postconstriction relaxation. The EFS-induced relaxation was endothelium independent and was greater (P < 0.01) in uterine arteries from pregnant than from nonpregnant patients. The relaxation was enhanced by guanethidine and superoxide dismutase, inhibited by nitric oxide synthase inhibitors, blocked by tetrodotoxin, and unaffected by atropine, propranolol, or indomethacin. The results demonstrate that human uterine arteries respond to EFS with contraction and relaxation and that these responses may be mediated, respectively, by norepinephrine and, in part, by nitric oxide released from periarterial nerves. The decrease in neuronally mediated uterine arterial constriction and the increase in dilation could be physiological mechanisms for ensuring appropriate uteroplacental perfusion.

Relaxation by calcitonin gene-related peptide may involve activation of K+ channels in the human uterine artery.

The vasodilatory role of calcitonin gene-related peptide in activating K+ channels was examined in isolated, suffused human uterine arteries. Calcitonin gene-related peptide produced a concentration-dependent relaxation of norepinephrine (1 microM)-induced contractions. Calcitonin gene-related peptide was antagonized by glybenclamide (1-100 microM), an inhibitor of ATP-sensitive K+ channels, but not by tetraethylammonium (1 mM), an inhibitor of calcium(2+)-activated K+ channels. Glybenclamide (10 microM) produced a 6.7 fold and an 11-fold shift to the right of calcitonin gene-related peptide (0.1 to 100 nM) in uterine arteries from pregnant patients (n = 3) and nonpregnant patients (n = 6), respectively. Calcitonin gene-related peptide (10 nM) less effectively (P < 0.05) relaxed contractions produced by KCl (50 mM) (29.4 +/- 1.6%) than by norepinephrine and glybenclamide (10 microM) did not reverse this relaxation (22.2 +/- 6.8%, n = 4 nonpregnant patients). Pinacidil (1 microM), an ATP-sensitive K+ channel opener, relaxed norepinephrine-induced contractions of uterine arteries. Glybenclamide (10 microM) also antagonized pinacidil. These results suggest that calcitonin gene-related peptide relaxes norepinephrine-contracted human uterine arteries, at least in part, by activation of a K+ channel, perhaps of the ATP-sensitive type.

Possible physiologic role of calcitonin gene-related peptide in the human uterine artery.

OBJECTIVE: The purpose of our study was to determine the potential physiologic role of calcitonin gene-related peptide as an endogenous vasodilator of human uterine arteries during pregnancy. STUDY DESIGN: Isolated, suffused uterine arteries from pregnant patients (n = 9) and nonpregnant patients (n = 19) were used in the study. RESULTS: Calcitonin gene-related peptide (1 nmol/L to 0.1 mumol/L) produced a concentration-dependent relaxation of norepinephrine (1 mumol/L)-induced contractions. The values of calcitonin gene-related peptide that inhibited norepinephrine-induced contractions by 50% were 0.9 +/- 0.7 nmol/L (n = 8) and 6.5 +/- 1.5 nmol/L (n = 12) in pregnant and nonpregnant arteries, respectively. The calcitonin gene-related peptide-induced relaxation was not affected by propranolol (1 mumol/L), indomethacin (5 mumol/L), methylene blue (10 mumol/L), or by the removal of the endothelium. The relaxant effect of calcitonin gene-related peptide was inhibited by human calcitonin gene-related peptide(8-37). The endogenous levels of calcitonin gene-related peptide were 110.2 +/- 13.5 pmol/L/gm wet weight in pregnant arteries and 14.8 +/- 3.2 pmol/L/gm wet weight in nonpregnant arteries. CONCLUSIONS: These results demonstrate that the vasodilatory effect of calcitonin gene-related peptide is mediated by calcitonin gene-related peptide1 receptors and does not involve beta-adrenoceptors, vasodilator prostanoids, increased levels of guanosine 3',5'-cyclic monophosphate, or endothelium-derived relaxing factor. The findings that calcitonin gene-related peptide acts as a potent dilator and that pregnancy increases both the sensitivity to calcitonin gene-related peptide and the endogenous levels of calcitonin gene-related peptide support the view that calcitonin gene-related peptide has a physiologic role in dilating the uterine vasculature, especially during pregnancy.

Vaginal birth after cesarean section at the University of Texas.

Vaginal delivery was successful in 76% of the 242 women who underwent a trial of labor after cesarean section in a prior pregnancy. Separation of the uterine scar occurred in four women (1.7%). Women whose prior cesarean section was for breech presentation had the highest rate of successful vaginal delivery (86%). The vaginal delivery rates were similar in women who delivered infants with birth weights > or = 4,000 g (73%) and < 4,000 g (76%). The use of epidural anesthesia and oxytocin may enhance the success of vaginal delivery in women undergoing a trial of labor following an earlier cesarean section.

Lack of reactivity of uterine arteries from patients with obstetric hemorrhage.

Obstetric hemorrhage may occur throughout pregnancy and the puerperium. The purpose of this study was to investigate the reactivity of isolated, suffused uterine arteries from obstetric patients with uncontrollable uterine bleeding and to compare those blood vessels with uterine arteries from patients undergoing cesarean hysterectomy for other medical reasons (control patients). The uterine arteries from the control patients (n = 9) responded with maximal or near-maximal constriction to norepinephrine (30 mumol/L, 3.6 +/- 1 gm), potassium chloride (75 mmol/L, 10.2 +/- 3 gm), prostaglandin F2 alpha (30 mumol/L, 1.8 +/- 1 gm), and arginine vasopressin (1 mumol/L, 18.8 +/- 2.6 gm). In uterine arteries from five patients with uncontrollable bleeding, the constrictor responses to the same drugs were markedly depressed: norepinephrine (30 mumol/L, 0.5 +/- 0.2 gm), potassium chloride (75 mmol/L, 1.9 +/- 0.8 gm); prostaglandin F2 alpha (30 mumol/L, 0 gm), and arginine vasopressin (1 mumol/L, 0.2 +/- 0.05 gm). Uterine arteries from two patients exhibited no constrictor responses to norepinephrine (30 mumol/L), potassium chloride (75 mmol/L), prostaglandin F2 alpha (30 mumol/L), or arginine vasopressin (1 mumol/L). The impaired responses to the vasoconstrictor drugs were not reversed by indomethacin (1 mumol/L), which is an inhibitor of prostaglandin synthetase; methylene blue (10 mumol/L), which is a blocker of endothelium-derived relaxing factor activation of guanylate cyclase; or propranolol (1 mumol/L), a beta-adrenergic receptor antagonist. The levels of adenosine 3':5'-cyclic monophosphate were not elevated in the uterine arteries from the patients with obstetric hemorrhage. The impaired reactivity to the multiple vasoconstrictors implies that a mechanism involved in constriction common to all of the constrictors is depressed or blocked. Furthermore, the depression or lack of reactivity of these isolated uterine arteries is not mediated by vasodilatory prostaglandins, endothelium-derived relaxing factor, beta-adrenergic receptors, or elevated levels of adenosine 3':5'-cyclic monophosphate. The results suggest that obstetric hemorrhage involves, in part, a lack of constrictor reactivity of the uterine vasculature.

Localized borderline lepromatous leprosy.

A 48-year-old soldier presented with 3 small leprosy lesions localized over the flexor area of the forearm. There was no nerve thickening and clinically the lesions looked like borderline-tuberculoid leprosy. However, these lesions demonstrated a bacteriological index (BI) of 4+ while no acid-fast bacilli (AFB) could be demonstrated from any other site of the body. A lepromin test was negative. Histologically evidence of borderline lepromatous leprosy was conspicuous. The case was diagnosed as localized borderline lepromatous-leprosy and treated with multidrug therapy. After 1 year of treatment, the lesions regressed, a lepromin test was positive (5 mm) and the BI from the lesions fell to 1+.

Magnesium sulfate-induced relaxation of uterine arteries from pregnant and nonpregnant patients.

The effects of magnesium sulfate at different concentrations were investigated in isolated rings of uterine arteries from pregnant and nonpregnant patients. Addition of magnesium sulfate (0.5 to 9.6 mmol/L) to the suffusion medium containing the normal concentration of 1.2 mmol/L magnesium sulfate produced concentration-dependent relaxation of norepinephrine (1 mumol/L)-induced or potassium chloride (35 mmol/L)-induced contractions. Magnesium sulfate was about three times more potent in causing inhibition of potassium chloride-induced contractions in uterine arteries from pregnant patients than in those from nonpregnant patients. The concentrations that inhibited 50% of the contraction induced by potassium chloride were 0.6 +/- 0.2 mmol/L (n = 4) in the arteries from pregnant patients and 1.6 +/- 0.2 mmol/L (n = 4) in the arteries from nonpregnant patients. At high concentrations (4.8 and 9.6 mmol/L), magnesium sulfate also was more potent in inhibiting norepinephrine-induced contractions in arteries from pregnant women than in arteries from nonpregnant women. The magnesium sulfate-induced relaxation was almost completely inhibited by calcium chloride (2 mmol/L) added to the suffusion medium containing the normal concentration of 2.5 mmol/L calcium chloride but was not affected by indomethacin (5 mumol/L), methylene blue (10 mumol/L), or removal of the endothelium. The results show that magnesium sulfate, at therapeutic blood concentrations, acts as a potent dilator of human uterine arteries, especially those from pregnant patients. The results are consistent with the view that magnesium sulfate may facilitate uteroplacental perfusion.

Comparison of nitroprusside and hydralazine in isolated uterine arteries from pregnant and nonpregnant patients.

The purpose of the present study was to determine the relative potency of nitroprusside and hydralazine with respect to inhibition of norepinephrine-induced contraction of isolated, uterine arteries from pregnant and nonpregnant patients. The arteries, obtained after hysterectomy, were dissected free from surrounding tissue, and arterial rings were prepared and mounted in tissue chambers filled with Kreb's-bicarbonate solution. Isometric tension was recorded. At concentrations of 10(-9) M to 10(-5) M, both nitroprusside and hydralazine produced concentration-dependent inhibition of the contractile response to norepinephrine. Nitroprusside and hydralazine were more potent in relaxing arteries contracted by a lower concentration (3 X 10(-6) M) of norepinephrine than by a higher concentration (10(-5) M) of norepinephrine. Regardless of the concentration of norepinephrine, nitroprusside was considerably more potent than hydralazine. The concentrations of nitroprusside that produced 50% inhibition (IC50) of the contractile response to norepinephrine (3 X 10(-6) M) in uterine arteries from pregnant and nonpregnant patients were 3.2 +/- 0.5 X 10(-9) M (n = 5) and 1.2 +/- 0.1 X 10(-9) M (n = 6), respectively. The IC50 values for hydralazine acting against norepinephrine (3 X 10(-6) M) in the uterine arteries from pregnant and nonpregnant patients were 5.1 +/- 0.5 X 10(-7) M (n = 5) and 4.0 +/- 0.5 X 10(-7) M (n = 6), respectively. Nitroprusside (10(-6) M), compared to hydralazine (10(-5) M), produced the greater maximal inhibition of norepinephrine-induced contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Pregnancy: increased effect of verapamil in human uterine arteries.

The effect of verapamil on the contractile response to norepinephrine in isolated, suffused uterine arteries from pregnant and nonpregnant humans was investigated. The arteries, obtained after hysterectomy, were dissected free from surrounding tissue and arterial rings were prepared and mounted in tissue chambers filled with Krebs-bicarbonate solution. Isometric tension was recorded. There was no significant difference between arteries from pregnant patients and arteries from nonpregnant patients when maximal contractile response and sensitivity to norepinephrine were compared. At concentrations of 0.3 and 3 microM, verapamil attenuated the response to norepinephrine in uterine arteries from both pregnant and nonpregnant patients. However, verapamil was significantly more potent in blocking the response to norepinephrine in arteries from pregnant patients.

Malignant hyperthermia: is etomidate safe?

The safety of etomidate for induction of anesthesia in malignant hyperthermia-susceptible (MHS) pigs was evaluated in a two-phase experiment. Two litters of Purebred Poland China pigs, one MHS (n = 4) and the other malignant hyperthermia-resistant (MHR) (n = 4) were used. Phase I compared MHS vs MHR animals in terms of cardiovascular, metabolic, and skeletal muscle rigidity responses to etomidate and fentanyl anesthesia and to a subsequent malignant hyperthermia (MH) challenge with halothane-succinylcholine. When three of the four criteria for the diagnosis of MH occurred (rigidity, tachycardia, or increases in temperature or end-tidal CO2) in an animal, phase I was terminated. In phase II, only the MHS animals were used and experimental procedures were as in phase I except thiopental replaced etomidate. In phase I, evidence was inadequate to support the diagnosis of MH based upon responses of MHS pigs to the infusion of etomidate even though the infusion of etomidate in MHS pigs was associated with statistically significant increases in body temperature and plasma lactate levels above those observed in MHR pigs. Heart rate and bicarbonate levels were lower in MHS than in MHR pigs during etomidate infusion. With discontinuation of etomidate and a subsequent challenge with halothane-succinylcholine, all four pigs developed the MH syndrome within 15-30 min. Thiopental replacement of etomidate in the phase II experiment resulted in a twofold greater time (45-75 min) for halothane-succinylcholine to trigger MH in the susceptible pigs.(ABSTRACT TRUNCATED AT 250 WORDS)