Real-Time Measurements of Gas-Phase Trichloramine (NCl3) in an Indoor Aquatic Center.

NCl3 is formed as a disinfection byproduct in chlorinated swimming pools and can partition between the liquid and gas phases. Exposure to gas-phase NCl3 has been linked to asthma and can irritate the eyes and respiratory airways, thereby affecting the health and athletic performance of swimmers. This study involved an investigation of the spatiotemporal dynamics of gas-phase NCl3 in an aquatic center during a collegiate swim meet. Real-time (up to 1 Hz) measurements of gas-phase NCl3 were made via a novel on-line derivatization cavity ring-down spectrometer and a proton transfer reaction time-of-flight mass spectrometer. Significant temporal variations in gas-phase NCl3 and CO2 concentrations were observed across varying time scales, from seconds to hours. Gas-phase NCl3 concentrations increased with the number of active swimmers due to swimming-enhanced liquid-to-gas transfer of NCl3, with peak concentrations between 116 and 226 ppb. Strong correlations between concentrations of gas-phase NCl3 with concentrations of CO2 and water (relative humidity) were found and attributed to similar features in their physical transport processes in pool air. A vertical gradient in gas-phase NCl3 concentrations was periodically observed above the water surface, demonstrating that swimmers can be exposed to elevated levels of NCl3 beyond those measured in the bulk air.

Chitayat syndrome: hyperphalangism, characteristic facies, hallux valgus and bronchomalacia results from a recurrent c.266A>G p.(Tyr89Cys) variant in the ERF gene.

BACKGROUND: In 1993, Chitayat et al., reported a newborn with hyperphalangism, facial anomalies, and bronchomalacia. We identified three additional families with similar findings. Features include bilateral accessory phalanx resulting in shortened index fingers; hallux valgus; distinctive face; respiratory compromise. OBJECTIVES: To identify the genetic aetiology of Chitayat syndrome and identify a unifying cause for this specific form of hyperphalangism. METHODS: Through ongoing collaboration, we had collected patients with strikingly-similar phenotype. Trio-based exome sequencing was first performed in Patient 2 through Deciphering Developmental Disorders study. Proband-only exome sequencing had previously been independently performed in Patient 4. Following identification of a candidate gene variant in Patient 2, the same variant was subsequently confirmed from exome data in Patient 4. Sanger sequencing was used to validate this variant in Patients 1, 3; confirm paternal inheritance in Patient 5. RESULTS: A recurrent, novel variant NM_006494.2:c.266A>G p.(Tyr89Cys) in ERF was identified in five affected individuals: de novo (patient 1, 2 and 3) and inherited from an affected father (patient 4 and 5). p.Tyr89Cys is an aromatic polar neutral to polar neutral amino acid substitution, at a highly conserved position and lies within the functionally important ETS-domain of the protein. The recurrent ERF c.266A>C p.(Tyr89Cys) variant causes Chitayat syndrome. DISCUSSION: ERF variants have previously been associated with complex craniosynostosis. In contrast, none of the patients with the c.266A>G p.(Tyr89Cys) variant have craniosynostosis. CONCLUSIONS: We report the molecular aetiology of Chitayat syndrome and discuss potential mechanisms for this distinctive phenotype associated with the p.Tyr89Cys substitution in ERF.

Exercise-mediated vasodilation in human obesity and metabolic syndrome: effect of acute ascorbic acid infusion.

We tested the hypothesis that infusion of ascorbic acid (AA), a potent antioxidant, would alter vasodilator responses to exercise in human obesity and metabolic syndrome (MetSyn). Forearm blood flow (FBF, Doppler ultrasound) was measured in lean, obese, and MetSyn adults (n = 39, 32 ± 2 yr). A brachial artery catheter was inserted for blood pressure monitoring and local infusion of AA. FBF was measured during dynamic handgrip exercise (15% maximal effort) with and without AA infusion. To account for group differences in blood pressure and forearm size, and to assess vasodilation, forearm vascular conductance (FVC = FBF/mean arterial blood pressure/lean forearm mass) was calculated. We examined the time to achieve steady-state FVC (mean response time, MRT) and the rise in FVC from rest to steady-state exercise (Δ, exercise - rest) before and during acute AA infusion. The MRT (P = 0.26) and steady-state vasodilator responses to exercise (ΔFVC, P = 0.31) were not different between groups. Intra-arterial infusion of AA resulted in a significant increase in plasma total antioxidant capacity (174 ± 37%). AA infusion did not alter MRT or steady-state FVC in any group (P = 0.90 and P = 0.85, respectively). Interestingly, higher levels of C-reactive protein predicted longer MRT (r = 0.52, P < 0.01) and a greater reduction in MRT with AA infusion (r = -0.43, P = 0.02). We concluded that AA infusion during moderate-intensity, rhythmic forearm exercise does not alter the time course or magnitude of exercise-mediated vasodilation in groups of young lean, obese, or MetSyn adults. However, systemic inflammation may limit the MRT to exercise, which can be improved with AA.

Neural control of blood flow during exercise in human metabolic syndrome.

α-Adrenergic-mediated vasoconstriction is greater during simulated exercise in animal models of metabolic syndrome (MetSyn) when compared with control animals. In an attempt to translate such findings to humans, we hypothesized that adults with MetSyn (n = 14, 35 ± 3 years old) would exhibit greater α-adrenergic responsiveness during exercise when compared with age-matched healthy control subjects (n = 16, 31 ± 3 years old). We measured muscle sympathetic nerve activity (MSNA; microneurography) and forearm blood flow (Doppler ultrasound) during dynamic forearm exercise (15% of maximal voluntary contraction). α-Adrenergic agonists (phenylephrine and clonidine) and an antagonist (phentolamine) were infused intra-arterially to assess α-adrenergic receptor responsiveness and restraint, respectively. Resting MSNA was ∼35% higher in adults with MetSyn (P < 0.05), but did not change in either group with dynamic exercise. Clonidine-mediated vasoconstriction was greater in adults with MetSyn (P < 0.01). Group differences in vascular responses to phenylephrine and phentolamine were not detected (P > 0.05). Interestingly, exercise-mediated vasodilatation was greater in MetSyn (P < 0.05). Adults with MetSyn exhibit greater resting MSNA and clonidine-mediated vasoconstriction, yet preserved functional sympatholysis and higher exercise blood flow during low-intensity hand-grip exercise when compared with age-matched healthy control subjects. These results suggest that adults with MetSyn exhibit compensatory vascular control mechanisms capable of preserving blood flow responses to exercise in the face of augmented sympathetic adrenergic activity.

Microvascular function in younger adults with obesity and metabolic syndrome: role of oxidative stress.

Older adults with cardiovascular disease exhibit microvascular dysfunction and increased levels of reactive oxygen species (ROS). We hypothesized that microvascular impairments begin early in the disease process and can be improved by scavenging ROS. Forearm blood flow (Doppler ultrasound) was measured in 45 young (32 ± 2 yr old) adults (n = 15/group) classified as lean, obese, and metabolic syndrome (MetSyn). Vasodilation in response to endothelial (ACh) and vascular smooth muscle [nitroprusside (NTP) and epoprostenol (Epo)] agonists was tested before and after intra-arterial infusion of ascorbic acid to scavenge ROS. Vasodilation was assessed as a rise in relative vascular conductance (ml·min(-1)·dl(-1)·100 mmHg(-1)). ACh and NTP responses were preserved (P = 0.825 and P = 0.924, respectively), whereas Epo responses were lower in obese and MetSyn adults (P < 0.05) than in lean controls. Scavenging of ROS via infusion of ascorbic acid resulted in an increase in ACh-mediated (P < 0.001) and NTP-mediated (P < 0.001) relative vascular conductance across all groups, suggesting that oxidative stress influences vascular responsiveness in adults with and without overt cardiovascular disease risk. Ascorbic acid had no effect on Epo-mediated vasodilation (P = 0.267). These results suggest that obese and MetSyn adults exhibit preserved endothelium-dependent vasodilation with reduced dependence on prostacyclin and are consistent with an upregulation of compensatory vascular control mechanisms.

Assessing the size and growth of the US wetland and stream compensatory mitigation industry.

Interest has focused on quantifying the size and scope of environmental markets, particularly those that offset ecosystem impacts or restore natural infrastructure to improve habitat or promote clean air and water. In this paper, we focus on the US wetland and stream compensatory mitigation market, asking: what types of firms make up the mitigation "industry"? What are the economic impacts-i.e., the "size"-of the mitigation industry? How has this industry changed over time? We present the results of a national survey of mitigation firms and construct an input-output model of the industry's economic impacts and employment. We also develop a comparative, 2014 model of the industry using data from a previous study of the broader, ecological restoration economy. Our findings suggest that the (2019, pre-COVID) mitigation industry collects annual revenues (direct economic impacts) in excess of $3.5 billion, which, along with additional indirect (supply chain) and induced (spillover) economic impacts, combine to over $9.6 billion in total output and support over 53,000 total jobs. We estimate 2014-2019 growth of ~35.2 percent in revenues, ~32.6 percent in total economic impacts, and a compound annual growth rate (CAGR) of 5.25%. This places the mitigation industry within the range of other, well-established industries within the technical services sector. We suggest establishing North American Industry Classification System (NAICS) codes specifically for ecological restoration and mitigation firms, an essential step in generating accurate and consistent employment estimates in the future, particularly at sub-national geographic scales.

Altered neurovascular control of the resting circulation in human metabolic syndrome.

Young healthy adults exhibit an inverse linear relationship between muscle sympathetic nerve activity (MSNA) and α-adrenergic responsiveness. This balance may be reversed in metabolic syndrome (MetSyn) as animal models exhibit increased sympathetic activity and α-mediated vasoconstriction. We hypothesized humans with MetSyn would demonstrate increased α-adrenergic vasoconstriction and the inverse relationship between MSNA and adrenergic responsiveness would be lost. We measured MSNA (microneurography of the peroneal nerve) and forearm blood flow (FBF, Doppler ultrasound) in 16 healthy control subjects (31 ± 3 years) and 14 adults with MetSyn (35 ± 3 years; P > 0.05) during local administration of α-adrenergic agonists (phenylephrine (PE), α(1); clonidine (CL), α(2)). MSNA was greater in MetSyn subjects than in healthy controls (P < 0.05). A group difference in vasoconstriction to PE was not detected (P = 0.08). The level of α(1)-mediated vasoconstriction was inversely related to MSNA in control subjects (r = 0.5, P = 0.04); this balance between MSNA and α(1) responsiveness was lost in adults with MetSyn. MetSyn subjects exhibited greater vasoconstriction to CL infusion as compared with healthy controls (P < 0.01). A relationship between MSNA and α(2)-mediated vasoconstriction was not detected in either group. In summary, altered neurovascular control in human MetSyn is receptor specific. The observed uncoupling between MSNA and α(1)-adrenergic responsiveness and increased α(2) vasoconstriction may lead to reduced FBF, altered flow distribution, and/or severe hypertension with the progression toward diabetes and cardiovascular disease.

Metaplastic sarcomatoid carcinoma of the breast appears more aggressive than other triple receptor-negative breast cancers.

Metaplastic sarcomatoid carcinoma (MSC) of the breast is usually triple receptor (ER, PR, and HER2) negative and is not currently recognized as being more aggressive than other triple receptor-negative breast cancers. We reviewed archival tissue sections from surgical resection specimens of 47 patients with MSC of the breast and evaluated the association between various clinicopathologic features and patient survival. We also evaluated the clinical outcome of MSC patients compared to a control group of patients with triple receptor-negative invasive breast carcinoma matched for patient age, clinical stage, tumor grade, treatment with chemotherapy, and treatment with radiation therapy. Factors independently associated with decreased disease-free survival among patients with stage I-III MSC of the breast were patient age > 50 years (P = 0.029) and the presence of nodal macrometastases (P = 0.003). In early-stage (stage I-II) MSC, decreased disease-free survival was observed for patients with a sarcomatoid component comprising ≥ 95% of the tumor (P = 0.032), but tumor size was the only independent adverse prognostic factor in early-stage patients (P = 0.043). Compared to a control group of triple receptor-negative patients, patients with stage I-III MSC had decreased disease-free survival (two-sided log rank, P = 0.018). Five-year disease-free survival was 44 ± 8% versus 74 ± 7% for patients with MSC versus triple receptor-negative breast cancer, respectively. We conclude that MSC of the breast appears more aggressive than other triple receptor-negative breast cancers.

Heterogeneous vascular responses to hypoxic forearm exercise in young and older adults.

We aimed to assess age-related differences in compensatory hypoxic vasodilation during moderate-to-high dynamic exercise at absolute workloads. We hypothesized healthy older adults (n = 12, 61 ± 1 years) would exhibit impaired hypoxic vasodilation at a moderate absolute workload, and this effect would be exaggerated at a higher workload when compared to young adults (n = 17, 27 ± 2 years). Forearm blood flow (FBF) was measured with Doppler ultrasound. Dynamic forearm exercise (20 contractions/min) was completed at two absolute workloads (8 and 12 kg) under normoxic (0.21 FiO2, ~98% SpO2) and isocapnic hypoxic (~0.10 FiO2, 80% SpO2) conditions performed in random order. FBF was normalized as forearm vascular conductance (FBF / mean arterial blood pressure = FVC) to control for differences in blood pressure and to assess vasodilation. FVC increased with exercise and hypoxia (main effects, p < 0.05); vascular responses were not different between young and older adults (interaction effect exercise × group p = 0.37 and hypoxia × group p = 0.96). Results were confirmed when analyzed as either an absolute or relative change in FVC (ΔFVC and %ΔFVC, respectively). Although group responses to hypoxia were not different, individual results were highly variable (i.e., some adults constricted and others dilated to hypoxia). These data suggest (1) compensatory hypoxic vasodilation in older adults is not impaired during forearm exercise at both moderate and higher absolute exercise intensities, and (2) vascular responses to hypoxia are heterogeneous in both young and older adults. Results suggest unique individual differences exist in factors regulating vascular responses to hypoxia.

Effect of obesity and metabolic syndrome on hypoxic vasodilation.

This study was designed to test whether obese adults and adults with metabolic syndrome (MetSyn) exhibit altered hyperemic responses to hypoxia at rest and during forearm exercise when compared with lean controls. We hypothesized blood flow responses due to hypoxia would be lower in young obese subjects (n = 11, 24 ± 2 years, BMI 36 ± 2 kg m(-2)) and subjects with MetSyn (n = 8, 29 ± 3 years BMI 39 ± 2 kg m(-2)) when compared with lean adults (n = 13, 29 ± 2 years, BMI 24 ± 1 kg m(-2)). We measured forearm blood flow (FBF, Doppler Ultrasound) and arterial oxygen saturation (pulse oximetry) during rest and steady-state dynamic forearm exercise (20 contractions/min at 8 and 12 kg) under two conditions: normoxia (0.21 F(i)O(2), ~98% S(a)O(2)) and hypoxia (~0.10 F(i)O(2), 80% S(a)O(2)). Forearm vascular conductance (FVC) was calculated as FBF/mean arterial blood pressure. At rest, the percent change in FVC with hypoxia was greater in adults with MetSyn when compared with lean controls (p = 0.02); obese and lean adult responses were not statistically different. Exercise increased FVC from resting levels in all groups (p < 0.05). Hypoxia caused an additional increase in FVC (p < 0.05) that was not different between groups; responses to hypoxia were heterogeneous within and between groups. Reporting FVC responses as absolute or percent changes led to similar conclusions. These results suggest adults with MetSyn exhibit enhanced hypoxic vasodilation at rest. However, hypoxic responses during exercise in obese adults and adults with MetSyn were not statistically different when compared with lean adults. Individual hypoxic vasodilatory responses were variable, suggesting diversity in vascular control.

Implications of group III and IV muscle afferents for high-intensity endurance exercise performance in humans.

We investigated the influence of group III/IV muscle afferents on peripheral fatigue, central motor drive (CMD) and endurance capacity during high-intensity leg-cycling. In a double-blind, placebo-controlled design, seven males performed constant-load cycling exercise (318 ± 9 W; 80% of peak power output (W(peak))) to exhaustion under placebo conditions and with lumbar intrathecal fentanyl impairing spinal µ-opioid receptor-sensitive group III/IV muscle afferents. Peripheral fatigue was assessed via changes in pre- vs. post-exercise quadriceps force in response to supramaximal magnetic femoral nerve stimulation (ΔQ(tw,pot)). CMD was estimated via quadriceps electromyogram. To rule out a direct central effect of fentanyl, we documented unchanged resting cardioventilatory responses. Compared to placebo, significant hypoventilation during the fentanyl trial was indicated by the 9% lower V(E)/V(CO(2)), causing a 5 mmHg increase in end-tidal P(CO(2)) and a 3% lower haemoglobin saturation. Arterial pressure and heart rate averaged 8 and 10% lower, respectively, during the fentanyl trial and these differences progressively diminished towards end-exercise. Although initially similar, the percent change in CMD was 9 ± 3% higher at end-exercise with fentanyl vs. placebo (P < 0.05). Time to exhaustion was shorter (6.8 ± 0.3 min vs. 8.7 ± 0.3 min) and end-exercise ΔQ(tw,pot) was about one-third greater (-44 ± 2% vs. -34 ± 2%) following fentanyl vs. placebo. The rate of peripheral fatigue development was 67 ± 10% greater during the fentanyl trial (P < 0.01). Our findings suggest that feedback from group III/IV muscle afferents limits CMD but also minimizes locomotor muscle fatigue development by stimulating adequate ventilatory and circulatory responses to exercise. In the face of blocked group III/IV muscle afferents, CMD is less inhibited but O(2) transport compromised and locomotor muscle fatigability is exacerbated with a combined net effect of a reduced endurance performance.

Opioid-mediated muscle afferents inhibit central motor drive and limit peripheral muscle fatigue development in humans.

We investigated the role of somatosensory feedback from locomotor muscles on central motor drive (CMD) and the development of peripheral fatigue during high-intensity endurance exercise. In a double-blind, placebo-controlled design, eight cyclists randomly performed three 5 km time trials: control, interspinous ligament injection of saline (5K(Plac), L3-L4) or intrathecal fentanyl (5K(Fent), L3-L4) to impair cortical projection of opioid-mediated muscle afferents. Peripheral quadriceps fatigue was assessed via changes in force output pre- versus postexercise in response to supramaximal magnetic femoral nerve stimulation (DeltaQ(tw)). The CMD during the time trials was estimated via quadriceps electromyogram (iEMG). Fentanyl had no effect on quadriceps strength. Impairment of neural feedback from the locomotor muscles increased iEMG during the first 2.5 km of 5K(Fent) versus 5K(Plac) by 12 +/- 3% (P < 0.05); during the second 2.5 km, iEMG was similar between trials. Power output was also 6 +/- 2% higher during the first and 11 +/- 2% lower during the second 2.5 km of 5K(Fent) versus 5K(Plac) (both P < 0.05). Capillary blood lactate was higher (16.3 +/- 0.5 versus 12.6 +/- 1.0%) and arterial haemoglobin O(2) saturation was lower (89 +/- 1 versus 94 +/- 1%) during 5K(Fent) versus 5K(Plac). Exercise-induced DeltaQ(tw) was greater following 5K(Fent) versus 5K(Plac) (-46 +/- 2 versus -33 +/- 2%, P < 0.001). Our results emphasize the critical role of somatosensory feedback from working muscles on the centrally mediated determination of CMD. Attenuated afferent feedback from exercising locomotor muscles results in an overshoot in CMD and power output normally chosen by the athlete, thereby causing a greater rate of accumulation of muscle metabolites and excessive development of peripheral muscle fatigue.

Calicivirus isolation and persistence in a pygmy chimpanzee (Pan paniscus).

What may be the first calicivirus isolate from any primate species, including man, was recovered from a herpesvirus-like lip lesion on a pygmy chimpanzee and then, 6 months later, from the throat of the same animal. The infected individual and its cage mates had circulating antibodies that were type-specific for this calicivirus. The agent was antigenically different from 30 other calicivirus serotypes and is tentatively designated primate calicivirus Pan paniscus type 1 (PCV-Pan 1).

Continuous infusion of enzyme replacement therapy is inferior to weekly infusions in MPS I dogs.

Intravenous enzyme replacement therapy with recombinant human α-L-iduronidase (rhIDU) is used weekly to treat mucopolysaccharidosis (MPS) I. We tested continuous administration of rhIDU at two dosing levels (0.58 mg/kg per week and 2 mg/kg per week) in MPS I dogs, and compared the efficacy of continuous infusion with the clinically used 0.58 mg/kg weekly three-hour infusion. Peak plasma concentrations of rhIDU were much higher in weekly-treated dogs (mean 256 units/ml) than steady-state concentrations in dogs treated with continuous infusion (mean 1.97 units/ml at 0.58 mg/kg per week; 8.44 units/ml at 2 mg/kg per week). Dogs receiving continuous IV rhIDU, even at a higher (2 mg/kg per week) dose, had consistently lower iduronidase levels in tissues than dogs receiving a weekly (0.58 mg/kg per week) dose. GAG storage was also less improved by continuous intravenous infusion. Adverse events were similar in all dosing groups. We found that continuous administration of 2 mg/kg per week rhIDU to MPS I dogs was insufficient to achieve GAG storage reduction comparable to 0.58 mg/kg weekly dosing.

Somatosensory feedback from the limbs exerts inhibitory influences on central neural drive during whole body endurance exercise.

We investigated whether somatosensory feedback from contracting limb muscles exerts an inhibitory influence on the determination of central command during closed-loop cycling exercise in which the subject voluntarily determines his second-by-second central motor drive. Eight trained cyclists performed two 5-km time trials either without (5K(Ctrl)) or with lumbar epidural anesthesia (5K(Epi); 24 ml of 0.5% lidocaine, vertebral interspace L(3)-L(4)). Percent voluntary quadriceps muscle activation was determined at rest using a superimposed twitch technique. Epidural lidocaine reduced pretime trial maximal voluntary quadriceps strength (553 +/- 45 N) by 22 +/- 3%. Percent voluntary quadriceps activation was also reduced from 97 +/- 1% to 81 +/- 3% via epidural lidocaine, and this was unchanged following the 5K(Epi), indicating the presence of a sustained level of neural impairment throughout the trial. Power output was reduced by 9 +/- 2% throughout the race (P < 0.05). We found three types of significant effects of epidural lidocaine that supported a substantial role for somatosensory feedback from the exercising limbs as a determinant of central command throughout high-intensity closed-loop cycling exercise: 1) significantly increased relative integrated EMG of the vastus lateralis; 2) similar pedal forces despite the reduced number of fast-twitch muscle fibers available for activation; 3) and increased ventilation out of proportion to a reduced carbon dioxide production and heart rate and increased blood pressure out of proportion to power output and oxygen consumption. These findings demonstrate the inhibitory influence of somatosensory feedback from contracting locomotor muscles on the conscious and/or subconscious determination of the magnitude of central motor drive during high intensity closed-loop endurance exercise.

Airway management.

The pediatric airway and respiratory function differ from those in adults. Optimum management requires consideration of these differences, but the application of adult principles is usually sufficient to buy time in an emergency until specialist pediatric help is available. Simple airway opening techniques such as head tilt and jaw thrust are usually sufficient to open the child's airway, but there is now a range of equipment available to bypass supraglottic airway obstruction-the strengths and weaknesses of such devices are explored in this article. The role of endotracheal intubation is also discussed, along with the pros and cons of the use of cuffed endotracheal tubes in children, and methods of confirming tracheal placement of the tube.

Clinical pharmacology of recombinant human tumor necrosis factor in patients with advanced cancer.

Twenty-six patients with advanced cancer refractory to standard therapy were treated with recombinant human tumor necrosis factor (rTNF) in a study aimed at determining the toxicity and tolerance of rTNF and at seeking evidence of antitumor activity. The study design involved two treatments per week for 4 weeks with alternating subcutaneous and intravenous (IV) administration, and weekly dose escalation through four levels in each patient. The dose range was 1 to 200 micrograms/m2 for IV bolus injection, and 5 to 250 micrograms/m2 for subcutaneous injection. Thirteen patients completed the full course. Early discontinuation of treatment was related to rTNF toxicity in seven cases. The major side effects were rigors, fever, headache, fatigue, and hypotension. Acute changes in granulocyte, lymphocyte, and monocyte counts, changes in serum zinc levels and plasma cortisol levels consistent with an acute phase response, and inflammation at the site of subcutaneous injection were also seen. At doses of 125 to 250 micrograms/m2, inflammation at the subcutaneous injection site was unacceptably severe. Minor changes were seen in hemostatic parameters. Hypotension was corrected by fluid administration and did not require treatment with vasopressors. Initial serum concentrations of rTNF were measured at five minutes after IV administration and were found to range from 2.5 ng/mL after a dose of 35 micrograms/m2 to 80 ng/mL after a dose of 200 micrograms/m2. The half-life of rTNF in the blood was 20 minutes. A decrease in lymph node size was observed in a patient with B cell lymphoma.

Drug-resistant and atypical mycobacterial disease. Bacteriology and treatment.

The treatment of drug-resistant mycobacterial disease requires excellent laboratory technology combined with an effective means of monitoring patients for drug toxicity and assuring patient compliance in treatment. Most tuberculosis is readily treated with easily administered, well-tolerated antituberculous combination medications such as isoniazid-ethambutol hydrochloride or isoniazid-rifampin. Primary drug-resistant tuberculosis is prevalent in many developing countries; drug resistance in the United States is generally acquired through inadequate or irregular drug ingestion. Drug-resistant tuberculosis and many "atypical" mycobacterioses required carefully designed drug regimens based on accurate drug susceptibility studies. Occasionally, patients with certain types of infection will have isolated pulmonary involvement for which surgical extirpation is beneficial. Despite the continued decline in the incidence of tuberculosis, atypical mycobacterial disease has remained constant and may eventually become the most prevalent mycobacteriosis in the United States.

Tuberculosis. A chemotherapeutic triumph but a persistent socioeconomic problem.

There is evidence that man has suffered from tuberculosis for more than 5,000 years, and through crowded living conditions, debilitation, and malnutrition, tuberculosis became epidemic in Western civilization and was a major cause of mortality. Identification of the tubercle bacillus as the causative agent in 1882 firmly established the infectious nature of the disease and the development of sanatoriums soon followed. Before the advent of effective chemotherapeutic agents, treatment involved rest, diet, and various surgical procedures, which were of little or no benefit to the patient. The discovery of dihydrostreptomycin, aminosalicylic acid, and isoniazid in the late 1940s and early 1950s meant that tuberculosis was now entirely curable in virtually all patients. Despite these effective chemotherapeutic and preventive agents, tuberculosis has receded to socioeconomically disadvantaged urban and rural areas, where the incidence parallels that of developing countries. Conquest of the disease will require improved health care delivery to the indigent and dispossessed.