ABSTRACT
OBJECTIVES: To determine clinical response of women with vulvar vestibulitis syndrome (VVS) to a hypocontactant vulvar skin regimen. MATERIALS AND METHODS: A clinical trial was conducted with 85 patients who met Friedrich's criteria for VVS. Pretreatment average duration of vulvar pain was 24 months. Of the 53 sexually active patients, 62% had Level II to III and 38% had Level I dyspareunia. All patients were treated with a hypocontactant vulvar skin regimen for a minimum of four months. Follow-up ranged 6 to 36 months. Follow-up clinical visits and questionnaires were used to determine the clinical effects. RESULTS: Six months following initiation of therapy, the response rate for reduction in vulvar pain was 77%-20% complete response, 57% partial response-and 23% no response. Additionally, 60% reported greater than or equal to one level of dyspareunia improvement. CONCLUSIONS: Contact irritants may be a factor causing vestibular pain in VVS patients.
ABSTRACT
The site and mode of action of acrylamide (ACR), gamma-diketone hexacarbons and 3',3'-iminodipropionitrile (IDPN) in producing a neurofilamentous axonopathy are unknown. Whether the neuropathy is caused by reduction in axonal transport produced by energy depletion is under investigation. Reductions in the quantity of proteins fast transported following a single dose of ACR or neurotoxic gamma-diketones have been reported. The current study examines the in vitro effects of these toxicants upon ATP production by mitochondria. Isolated rat brain mitochondria incubated for 30 min at 37 degree C with neurotoxic doses of ACR (0.7 mM) or 3,4-dimethyl-2,5-hexanedione (0.25 mM) retained similar capacities for synthesis of ATP from pyruvate and endogenous concentrations of ATP compared to controls. 2,5-Hexanedione (2,5-HD; 4 mM) and IDPN (0.1%) significantly reduced the rate of synthesis (-22.5% and -15%, respectively); but only 2,5-HD decreased the endogenous concentration of ATP (-21.6%) following a single 30 min exposure. Toxicant action on ATP production is limited to 2,5-HD; the correlation between the toxicant-induced changes in axonal transport and mitochondrial ATP production demonstrate the necessity to evaluate other structures as the critical site of action in producing axonal transport changes.
Subject(s)
Adenosine Triphosphate/metabolism , Axons/ultrastructure , Brain/enzymology , Mitochondria/enzymology , Neurotoxins/pharmacology , Peripheral Nervous System Diseases/metabolism , Animals , Intermediate Filaments/pathology , Kinetics , Male , Neurotoxins/metabolism , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/pathology , Rats , Rats, Inbred StrainsABSTRACT
The purpose of this investigation was to examine eccrine sweat gland responsiveness to intradermal injections of methylcholine (MCh) across three age groups of men [young (Y) = 22-24; middle (M) = 33-40; older (O) = 58-67 yr old, n = 5 per group]. Subjects were matched with respect to maximum O2 consumption, body size, and body composition, and were thoroughly heat acclimated before participation. Randomly ordered concentrations of acetyl-beta-methylcholine chloride ranging from 0% (saline) to 0.1% (5 x 10(-3) M) were injected into the skin of the dorsal thigh in a thermoneutral environment, and activated sweat glands were photographed at 30-s intervals for the next 8 min. Density of MCh-activated glands was independent of both age and [MCh] (e.g., 2 min after injection of 5 x 10(-3) M [MCh]: Y = 45 +/- 7, M = 46 +/- 12, O = 42 +/- 5 glands/cm2). However, sweat gland output (SGO) per active gland was significantly lower for the O group and failed to increase with increasing [MCh] above 5 x 10(-4) M. When MCh (5 x 10(-3) M) was injected after 1 h of exercise in the heat, higher SGO's were elicited in each group; however, the SGO of the O group was again significantly lower than that of the Y group (91 +/- 11 vs. 39 +/- 4 ng/gland, P less than 0.02) with the M group intermediate (69 +/- 11 nl/gland; 2 min postinjection data).(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Aging/physiology , Choline/analogs & derivatives , Eccrine Glands/drug effects , Sweat Glands/drug effects , Adult , Aged , Choline/pharmacology , Eccrine Glands/anatomy & histology , Eccrine Glands/metabolism , Humans , Male , Middle Aged , Sweat/drug effects , Sweat/metabolismABSTRACT
When work is performed by workers in protective clothing, sweat evaporation is limited and body temperature rises. In an attempt to quantify the limits such ensembles place on safe work, 6 acclimated men and women walked at 30% VO2max (150-200 W/m2) in 2 protocols involving environmental transients. In one, ambient water vapor pressure (Pw) was fixed at 10 torr, and after rectal temperature (Tre) plateaued, ambient dry-bulb temperature (Tdb) was raised 2 degrees C every 10 min. In the second, Tdb was constant and Pw was increased 2 torr every 10 min. Critical temperature (Tcrit) and pressure (Pcrit) were defined as the Tdb or Pw at which thermal balance could no longer be maintained and Tre rose sharply. Each test was performed in various clothing ensembles ranging from light cotton work clothes to "impermeable" suits. Lines connecting mean Tcrit and mean Pcrit define a limit for safe prolonged exposure/exercise for approximately 50% of the population in each ensemble. Similar lines, drawn to represent values 2 standard deviations below the mean, should provide critical environmental limits for 95% of the population.
Subject(s)
Physical Exertion , Protective Clothing , Body Temperature , Female , Humans , Male , Maximum Allowable Concentration , Psychometrics , Time FactorsABSTRACT
When work is performed in heavy clothing, evaporation of sweat from the skin to the environment is limited by layers of wet clothing and air. The magnitude of decrement in evaporative cooling is a function of the clothing's resistance to permeation of water vapor. A physiological approach has been used to derive effective evaporative coefficients (he) which define this ability to evaporate sweat. We refined this approach by correcting the critical effective evaporative coefficient (K for sweating efficiency (Ke,eta') since only a portion of the sweat produced under such conditions is evaporated through the clothing. Six acclimated men and women walked at 30% maximal O2 consumption (150-200 W.m-2) at a constant dry bulb temperature as ambient water vapor pressure was systematically increased 1 Torr every 10 min. Critical pressure was defined as the partial pressure of water vapor (Pw) at which thermal balance could no longer be maintained and rectal temperature rose sharply. Each test was performed in various clothing ensembles ranging from cotton shirt and pants to "impermeable" suits. This approach was used to derive he by solving the general heat balance equation, M - W +/- (R + C) = w.he.(Psk - Pw), where M is metabolic heat production, W is external work, R is radiant heat exchange, C is convective heat transfer, w is skin wettedness, and Psk is water vapor pressure of fully wet skin.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Body Temperature Regulation , Physical Exertion , Protective Clothing , Water Loss, Insensible , Acclimatization , Adult , Body Temperature , Female , Heart Rate , Humans , Male , Skin TemperatureABSTRACT
A series of studies was performed in which Syrian golden hamsters were injected intratracheally with 25 to 200 micrograms of highly purified human C5 or the 200,000 molecular weight form of trypsin-activated C5 (C5'). Bronchoalveolar lavage (BAL) was performed 4 h after intratracheal injection, the recovered white cells were counted and differentiated, and the BAL fluid was assayed for in vitro neutrophil chemotactic activity. A significant increase in BAL neutrophils and total BAL cell numbers was evident at 4 h after C5' instillation. In contrast, highly purified native C5 induced no evidence of pulmonary inflammation, even at the highest injection doses studied. Kinetic experiments indicated that hamsters receiving an intratracheal injection of 60 micrograms of C5' per animal demonstrated rapid pulmonary neutrophil infiltration that persisted for 120 to 168 h. Control hamsters receiving intratracheal injections of phosphate-buffered saline (PBS) or 60 micrograms of highly purified C5 did not demonstrate significant neutrophil infiltration. Lung pathology studies revealed neutrophilic alveolitis with intraalveolar and intracapillary neutrophil infiltration in the C5'-treated animals. The BAL fluid obtained from C5'-treated, but not from C5-treated or control hamsters, contained chemotactic factors for neutrophils, which appeared to be unrelated to C5. From these studies we conclude that C5', the 200,000 molecular weight form of protease-activated C5, is capable of mediating an acute inflammatory response in the hamster lung in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Complement Activation , Complement C5 , Pneumonia/etiology , Trypsin/pharmacology , Animals , Chemotaxis, Leukocyte , Cricetinae , Female , Lung/pathology , Mesocricetus , Neutrophils/analysis , Pneumonia/pathology , Therapeutic IrrigationABSTRACT
Bacterial pneumonia is a common complication of lung injury that can be an important determinant of outcome. We studied experimental lung injury produced in hamsters by injecting 20 mg/kg paraquat (PQ) intraperitoneally; control animals received saline vehicle. Three days later, Pseudomonas aeruginosa (PAO1), 10(8) organisms in 0.25 ml, or saline, 0.25 ml, was inoculated intratracheally. Lung and systemic antibacterial defenses were studied at death 24 h later. Paraquat alone produced focal interstitial pneumonitis and neutrophilic alveolitis, and resulted in a 12% (3 of 26) mortality. PAO1 alone caused focal pneumonias and no deaths. Animals receiving both agents (PAO1/PQ) had extensive diffuse alveolar damage characterized by alveolar hemorrhage, edema, influx of neutrophils, and vasculitis; 50% (16 of 32) died within 96 h of PQ injection. Mean lung counts of PAO1 at death were 7.6 X 10(4) colony forming units/g in PAO1 and 2.8 X 10(7) in PAO1/PQ animals (p less than 0.05). PAO1 colony counts in liver were increased nearly 100-fold in PAO1/PQ animals (p less than 0.05). Half-time of clearance of P. aeruginosa from the blood was prolonged in PAO1 and in PAO1/PQ animals (p less than 0.05) but not in PQ animals. Phagocytosis of Staphylococcus aureus by leukocytes lavaged from the lung was not impaired in any group compared with that in control animals, but intracellular killing was impaired in PAO1 and PAO1/PQ but not in PQ animals. Paraquat injury impairs lung antibacterial defenses by uncertain mechanisms. Superinfection of PQ-injured lungs by PAO1 appears responsible for defects in intrapulmonary and systemic antibacterial defenses.
Subject(s)
Pneumonia/immunology , Pseudomonas Infections/immunology , Respiratory Distress Syndrome/immunology , Animals , Blood Bactericidal Activity , Cricetinae , Female , Leukocytes/immunology , Lung/immunology , Paraquat , Phagocytosis , Pneumonia/complications , Pseudomonas Infections/complications , Respiratory Distress Syndrome/chemically induced , Respiratory Distress Syndrome/complications , Staphylococcus aureus/immunology , Time FactorsABSTRACT
A mononuclear cell chemoattractant of high specific activity produced by baboon (Papio cynocephalus) aortic medial smooth-muscle cells (SMCs) in culture has been partially characterized. Smooth-muscle cells, between the third and eighth passage, were grown to confluence in Medium 199 containing 10% fetal calf serum and then incubated for 24 hours in either serumless medium (Neuman and Tytell) or Medium 199 containing 0.2% bovine serum albumin. The 24-hour SMC-conditioned medium was fractionated on Sephadex G100-Superfine and potent chemoattractant activity (SMC-CF) eluted in the 10,000-12,000 dalton region. SMC-CF displayed chemotactic and chemokinetic activity for peripheral blood mononuclear cells but not for polymorphonuclear leukocytes. Production of SMC-CF by the cells was significantly inhibited in the presence of cycloheximide, and its activity was abolished after incubation with the bacterial protease subtilisin. Chromatofocusing experiments indicate that SMC-CF is a cationic protein with a pI of greater than 10.5. The role of SMC-CF may play as an inflammatory mediator in monocyte recruitment to the arterial intima in atherogenesis is discussed.
Subject(s)
Chemotactic Factors/isolation & purification , Monocytes/metabolism , Muscle, Smooth, Vascular/cytology , Animals , Chemotactic Factors/biosynthesis , Chemotactic Factors/physiology , Chemotaxis, Leukocyte/drug effects , Cycloheximide/pharmacology , Interleukin-8 , Molecular Weight , Monocytes/physiology , Muscle, Smooth, Vascular/metabolism , Neutrophils/physiology , Papio , Peptide Hydrolases/pharmacologyABSTRACT
Levamisole, an anthelminthic agent with immunostimulatory properties, does not alter in vitro macrophage-lymphocyte rosette formation between sheep alveolar macrophages and autochthonous lymphocytes.