Search

A critical step in profitable post-harvest potato storage management is to cure tubers at appropriate temperatures long enough for rapid wound-healing to prevent disease and defect development, but not too long to jeopardize storage quality. A two-year storage study was conducted in macro-storage totes at the University of Wisconsin Hancock storage research facility to evaluate the effects of higher wound-healing temperatures (15.6 &deg, C, 18.3 &deg, C) imposed for different durations, and compare them to the U.S. potato industry&rsquo, s standard practice (12.8 &deg, C), on weight loss and frying quality of multiple processing potato varieties during long-term storage. It was found that in the experimental setting of this study, warmer wound-healing temperatures resulted in (1) less weight loss, particularly during the early storage season across varieties, (2) ameliorated senescent sweetening of the Snowden variety, (3) improved fry quality of the Russet Burbank variety, (4) and no apparent disease spread during long-term storage if tubers were harvested healthy out of fields. Overall, no significant difference was found between 15.6 &deg, C and 18.3 &deg, C regarding their treatment effects. Our conclusion is that compared to the current standard practice, higher wound-healing temperatures may have the potential benefits of improving potato storage quality while reducing the economic penalty associated with weight loss for specific varieties, but tubers should be healthy at harvest in order to gain the benefits. Further research is needed to test if those benefits of higher wound-healing temperatures hold true in large-scale commercial storage facilities.

The literature has been reviewed for contact dermatitis from topical antiviral drugs. 15 agents have been identified including acyclovir, imiquimod, podophyllin, podofilox, cidofovir, penciclovir, vidarabine, idoxuridine, trifluridine, tromantadine, lamivudine, interferon intralesional injections and ophthalmic solution, fomivirsen and foscarnet intravitreal injections and ganciclovir intraocular implants. Patch testing has been documented in certain individuals and cross-sensitization has been observed to contribute significantly to some allergic reactions.

A review of the literature has identified 10 agents causing contact dermatitis among topically administered drugs for glaucoma. These agents include beta-blockers (timolol, befunolol, betaxolol, levobunolol, carteolol, metipranolol), a carbonic anhydrase inhibitor (dorzolamide), a parasympathomimetic (pilocarpine), and sympathomimetics (dipivefrin, apraclonidine). Patch testing has been documented in certain individuals as well as cross sensitization and reactivity. Systemic reactions to these topically applied medications have been briefly noted.

N-Acetylcysteine is useful as a mucolytic agent for treatment of chronic bronchitis and other pulmonary diseases complicated by the production of viscous mucus. It is also used as an antidote to paracetamol (acetaminophen) poisoning and found to be effective for the prevention of cardiotoxicity by doxorubicin and haemorrhagic cystitis from oxazaphosphorines. After an oral dose of N-acetylcysteine 200 to 400 mg the peak plasma concentration of 0.35 to 4 mg/L is achieved within 1 to 2 hours. Although the data are conflicting, it appears that the administration of charcoal may interfere with drug absorption, with up to 96% of the drug adsorbed on to the charcoal. Information on absorption in the presence of food or other drugs is not available. The volume of distribution ranges from 0.33 to 0.47 L/kg and protein binding is significant, reaching approximately 50% 4 hours after the dose. Pharmacokinetic information is not available as to whether or not N-acetylcysteine crosses the blood-brain barrier or placenta, or into breast milk. Renal clearance has been reported as 0.190 to 0.211 L/h/kg and approximately 70% of the total body clearance is nonrenal. Following oral administration, reduced N-acetylcysteine has a terminal half-life of 6.25h. Little is known of the metabolism of this agent, although it is believed to be rapidly metabolised and incorporated on to proteins. The major excretory product is inorganic sulphate. Frequently reported side effects are nausea, vomiting and diarrhoea. Biochemical and haematological adverse effects are observed but are not clinically relevant. Drug interactions of clinical significance have been observed with paracetamol, glutathione and anticancer agents.

To determine whether close collaboration between a neck ultrasound-certified endocrinologist and a skilled endocrine surgeon can optimize minimally invasive radio-guided parathyroidectomy (MIRP) surgical outcomes.Outcome data were collected on patients with primary hyperparathyroidism whom we intended to treat with MIRP at the induction of anesthesia between October 1, 2005, and December 31, 2007. Patients underwent preoperative gamma camera sestamibi scanning (GCSS), intraoperative gamma probe sestamibi scanning (IOSS), and preoperative neck ultrasonography. Intraoperative parathyroid hormone (PTH) monitoring was performed. Postoperative surgical success was defined as a serum calcium concentration between 8.0 and 10.4 mg/dL within 4 weeks of surgery.During the study period, MIRP was planned for 46 patients. Of the 46 patients, 39 had preoperative neck ultrasonography; 7 underwent evaluation by an endocrinologist or internist who was not ultrasound certified and they therefore did not undergo preoperative ultrasonography. IOSS correctly identified 1 adenomatous gland in 38 of 46 patients (83%), while GCSS correctly localized 1 adenomatous gland in 30 of 46 patients (65%). In 11 GCSS-negative patients, IOSS identified the abnormal gland in 7 (64%), while ultrasonography identified the abnormal gland in 8 (73%). The surgical approach was converted to traditional parathyroidectomy in 3 patients. Every patient exhibited at least a 51% drop in intraoperative PTH levels with resection of the final adenoma; average decrement for the entire group was 79 +/- 8% from the highest baseline level. Forty-five patients (98%) demonstrated sustained normalization of serum calcium within several days of surgery.A collaborative endocrinology and surgical endocrine oncology practice arrangement, emphasizing careful preoperative physician-supervised neck ultrasonography and the use of intraoperative PTH measurement, optimizes MIRP outcomes.

This article examines the detection, assessment, and therapeutic modalities available for tuberculosis meningitis. Without appropriate treatment this disease is fatal within 2 months of development, and mortality is closely associated with the stage of disease upon initiation of chemotherapy. Initial lumbar puncture reveals smear-positive acid-fast bacilli in up to 40% in most series; however, repeat examinations increase the yield, via direct smear, to as high as 87%. Analysis of cerebrospinal fluid is described, along with advanced techniques for early detection of this infection. Eight antituberculosis agents have known penetration into the cerebrospinal fluid. The most important prognostic factor is the neurological stage at which the individual presents at the initiation of therapy. Various chemotherapeutic approaches are available but it appears the use of rifampicin (rifampin) with isoniazid-containing regimens gives the best results. Regardless of the therapy undertaken, a significant number of individuals are left with some degree of neurological deficit. The roles of bacillus of Calmette and Guérin (BCG) vaccine, steroids, and neurosurgery in the treatment of this disease are also discussed.

The authors report a case of endometriosis that presented as a cystic mass in the tail of the pancreas, leading to extensive evaluation and ultimately a major surgical resection. The diagnosis was made by histopathological evaluation, revealing endometrial glands and stroma in the wall of the mass with hemorrhagic fluid in the cystic lumen, compatible with pancreatic involvement by an endometrial cyst.

This case report describes a rare dermatologic reaction in a patient after administration of pneumococcal vaccine. A 65-year-old man developed an extensive dermatitis with pruritus, urticaria, and petechiae 1 week after receiving an intramuscular injection o the vaccine. The reaction resolved with application of topical steroids and oral diphenhydramine hydrochloride. This case report and others in the literature suggest the importance of recognizing the possibility of cutaneous adverse reactions with vaccines, such as the pneumococcal vaccine, which in general have a good safety profile.

Corynebacterium minutissimum is the bacteria that leads to cutaneous eruptions of erythrasma and is the most common cause of interdigital foot infections. It is found mostly in occluded intertriginous areas such as the axillae, inframammary areas, interspaces of the toes, intergluteal and crural folds, and is more common in individuals with diabetes mellitus than other clinical patients. This organism can be isolated from a cutaneous site along with a concurrent dermatophyte or Candida albicans infection. The differential diagnosis of erythrasma includes psoriasis, dermatophytosis, candidiasis and intertrigo, and methods for differentiating include Wood's light examination and bacterial and mycological cultures. Erythromycin 250mg four times daily for 14 days is the treatment of choice and other antibacterials include tetracycline and chloramphenicol; however, the use of chloramphenicol is limited by bone marrow suppression potentially leading to neutropenia, agranulocytosis and aplastic anaemia. Further studies are needed but clarithromycin may be an additional drug for use in the future. Where there is therapeutic failure or intertriginous involvement, topical solutions such as clindamycin, Whitfield's ointment, sodium fusidate ointment and antibacterial soaps may be required for both treatment and prophylaxis. Limited studies on the efficacy of these medications exist, however, systemic erythromycin demonstrates cure rates as high as 100%. Compared with tetracyclines, systemic erythromycin has greater efficacy in patients with involvement of the axillae and groin, and similar efficacy for interdigital infections. Whitfield's ointment has equal efficacy to systemic erythromycin in the axillae and groin, but shows greater efficacy in the interdigital areas and is comparable with 2% sodium fusidate ointment for treatment of all areas. Adverse drug effects and potential drug interactions need to be considered. No cost-effectiveness data are available but there are limited data on cost-related treatment issues. A guideline is proposed for the detection, evaluation, treatment and prophylaxis of this cutaneous eruption.

The successful treatment of a large sacral pressure sore with calcium sodium alginate dressings is described

The literature was reviewed for cases of cutaneous pigmentation induced by rifampicin overdosage. 29 examples have been described, in which 2 general groups of individuals were observed. The first consisted of older individuals (average age 27.1 years) who attempted suicide. A prior history of suicide attempts, depression and substance abuse was a predominant factor in these patients. The second group included generally younger patients (average age 2.9 years) in whom misformulation of rifampicin preparations for treatment of Haemophilus influenzae Type B resulted in bright reddish-orange discoloration to the skin. The time to clinical appearance of skin discoloration was approximately 2.2 hours after administration. Periorbital or facial oedema occurred in 72.4% of the patients, pruritus in 62.1% and either nausea, vomiting or diffuse abdominal tenderness in 51.7%. Limited laboratory data are available but these indicate that all patients had elevated levels of total bilirubin. Histological examination in selected individuals revealed rifampicin crystal deposits in the nasopharynx, gastrointestinal tract and lining of the aorta. In adults, it appears that a dose of at least 14 g of rifampicin is necessary before cardiovascular-pulmonary arrest occurs. Other than general supportive measures, very few methods are described in the literature for the treatment of acute intoxications with this drug. A differential diagnosis of other causes of reddish-orange pigmentation is discussed, together with clinical information to differentiate these cases from toxic rifampicin ingestion.

A modification of the spectrofluorimetric method of Lowe et al 1 for the measurement of glutamic acid decarboxylase (GAD) activity in rat brain is described. This method involves the indirect determination of GAD activity by measurement of the formation of gamma-amino-butyric acid (GABA). The minimum activity of GAD observable was 0.45 μg GABA/hour/mg protein and the limit of detection was 0.20 × 10−6 M GABA. This method was developed for measurement of GAD activity of gabaergic terminals in globus pallidus, endopeduncular nucleus, substantia nigra, and ventromedial thalamus in rat brain.

A quantitative high pressure liquid chromatographic (HPLC) assay has been developed for the determination of isoniazid (INH) and acetylisoniazid (ACINH) in human plasma. Plasma samples were taken from a patient after oral administration of INH (with proven tuberculosis infection). A C18 reversed phase radial compression column was used to separate INH and ACINH from other plasma components. The analysis takes 10 minutes per sample and the lower limit of detection for each compound is 0.10 ug/ml plasma.

The literature has been reviewed for contact dermatitis occurring to antituberculosis agents. Of the 12 known drugs. 6 (isoniazid, rilfampicin. Ethamnbutol, para-aminosalicylic acid. streptomycin and kanamycin) have been documented by punch test to cause this type of dermatitis in certain individuals. Cross sensitization has been observed to contribute significantly to the allergic reactions noted from isoniazid, streptomycin, and kanamycin. Hyposensitization has also been discussed in this review.

An analytical method has been developed for the determination of N-acetylcysteine in human serum following acetaminophen overdosage in humans. Serum samples were treated with dithiothreitol and the protein-freed product was derivatized with 2,4-dinitrofluorobenzene. N-Acetylhomocysteine thiolactone was used as an internal standard. Following diethyl ether extraction, the components were separated on a reversed-phase column with retention times of 7.4 and 9.9 min for N-acetylcysteine and internal standard, respectively. Ultraviolet detection at 365 nm was employed and little interference was noted from other serum components. The method has been applied to quantitation of N-acetylcysteine given as treatment for acetaminophen intoxication.

The neurological manifestations and toxicities of 12 antituberculosis drugs [isoniazid, rifampicin (rifampin), ethambutol, p-aminosalicylic acid, pyrazinamide, streptomycin, kanamycin, ethionamide, cycloserine, capreomycin, viomycin and thiacetazone] are reviewed. Their effects upon the central nervous system, cranial nerves, peripheral nerves and the neuromuscular junction are examined, and drug interactions of neurological concern are briefly discussed. Isoniazid is well known to increase the concentrations of gamma-aminobutyric acid in neural tissues. Although conflicting data have been published, isoniazid may play a limited future role in reducing the degree of adventitious movements noted in certain neurological diseases such as multiple sclerosis, spasmodic torticollis, and other segmental dystonic syndromes. With rifampicin neurological complications have been observed infrequently. Rifampicin penetrates into the CSF and has been shown to have useful activity against various micro-organisms in the CSF, including certain viruses; however, contrary to earlier suggestions, it appears to have no role in the treatment of subacute sclerosing panencephalitis. A number of studies have indicated that isoniazid is associated with a large number of accidental and intentional poisonings. The highest incidence has been observed with Southwestern American Indians in which this agent was involved in 7% of all suicide attempts and 19% of the suicide deaths. Degeneration of the optic chiasma and nerve is a well-known adverse effect of ethambutol; toxicity is manifested by impairment of visual acuity, marked loss of colour discrimination, constricted visual fields, and central and peripheral scotoma. Ototoxicity is a well known problem caused by streptomycin, kanamycin, capreomycin and viomycin. The use of streptomycin in pregnant mothers is associated with congenital deafness in newborns in certain cases. The aminoglycoside antibiotics are also associated with flaccid paralysis following neuromuscular blockade. Adverse reactions to cycloserine are mainly dose-related with neurological and psychiatric syndromes noted in up to 50% of patients. Recent data indicate that isoniazid, rifampicin, ethambutol, pyrazinamide, streptomycin, kanamycin, ethionamide, and cycloserine appear in measurable quantities in the cerebrospinal fluid. Five of these compounds (isoniazid, rifampicin, ethambutol, kanamycin, cycloserine) pass to some degree through non-inflamed meninges. Other than discontinuation of the therapeutic regimen and general supportive measures, very few methods are described in the literature for treatment of acute intoxications with antituberculosis drugs.

Blood dyscrasias comprise 10 % of the total number of drug induced adverse affects and account for approximately 40 % of fatal reactions related to drug administration 11, 21. Antituberculosis agents have been reported to produce a wide range of haematological side effects. In this paper the documented cases of haematologic abnormalities induced by 12 antituberculosis compounds (isoniazid, rifampicin, ethambutol, para-aminosalicylic acid, pyrazinamide, streptomycin, kanamycin, ethionamide, capreomycin, viomycin, cycloserine and thiacetazone) will be reviewed, along with possible mechanisms of action and any known methods of treatment.

Two procedures using liquid chromatography with electrochemical detection are described for the determination of dopamine (DA) and its two acidic metabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), in subregions of rat striatum and nucleus accumbens. A strong cation-exchange column was used for DA analysis and a C18 reversed-phase column was used for the analysis of the metabolites. Effects of pH, temperature and percentage of methanol on the retention time of HVA and DOPAC were studied. Levels of these compounds in the subregions of rat stratum and nucleus accumbens are reported.

The quantitative aspects of the disposition in man of 12 antituberculosis drugs [isoniazid, rifampicin, (rifampin), ethambutol, para-aminosalicylic acid, pyrazinamide, streptomycin, kanamycin, ethionamide, cycloserine, capreomycin, viomycin and thiacetazone] are reviewed. Isoniazid appears to be the only agent for which plasma concentrations and clearance are related to hereditary differences in acetylator status and for which there is an appreciable 'first-pass' effect. Recent data cast doubt on the suggestion that isoniazid may be more hepatotoxic for rapid as opposed to slow acetylators. Continuous administration of rifampicin leads to induction of enzymes in the liver with a concomitant decrease in maximum plasma concentrations, the time required to achieve this level, elimination half-life, and area under the plasma concentration-time curve (AUC). Coadministration of para-aminosalicylic acid leads to increases in the serum concentrations and elimination half-life of isoniazid. With a few exceptions, the metabolites of the antituberculosis drugs are devoid of antimicrobial activity; the exceptions are 25-desacetylrifampicin which accounts for approximately 80% of the drug's antimicrobial activity in human bile, the acetylated and glycylated metabolites of para-aminosalicylic acid, and the sulphoxide metabolites of ethionamide. The effect of renal impairment is relatively unimportant for the excretion of isoniazid, rifampicin and para-aminosalicylic acid, but the elimination half-life of streptomycin increases to 100 hours when the blood urea nitrogen level is greater than 100mg/100ml, and ototoxicity is strikingly more frequent. In states of malnutrition, such as kwashiorkor, the protein binding of para-aminosalicylic acid decreases from 15% to essentially zero and in the case of ethionamide and streptomycin binding decreases by 6% and 16% respectively. Of the data concerning age-related effects, most notable are the prolonged elimination half-life of isoniazid in neonates (up to 19.8 hours), and the lower peak serum concentrations of rifampicin in children of one-third to one-tenth those of adults following a similar dose on a weight basis. For kanamycin, the maximum plasma concentration varies inversely with age but is not influenced by birthweight; however, the clearance is directly dependent upon birthweight and postnatal age. For the elderly, age is an insignificant factor for the elimination of isoniazid when compared with young adults of similar acetylator status, and the metabolism of rifampicin may be considered globally unaltered in this age group.(ABSTRACT TRUNCATED AT 400 WORDS)

The teratogenic effects of twelve antituberculosis drugs in animal models and man are reviewed. A number of congenital malformations have been associated with the use of these agents; however, for the most part, the birth defect rate is not above that expected for the normal population. Isoniazid and ethambutol are considered the safest for maternal use. Although rifampicin appears to be more problematic, if the disease is severe or extensive, it may be added, preferably after the first trimester. Streptomycin and kanamycin are associated with eighth cranial nerve damage and should be avoided if possible during cyesis. At least five of these compounds have documented evidence of transplacental passage. In consideration of the number of drugs that are available for treatment, routine therapeutic abortions in pregnant females with tuberculosis is not medically indicated.

A quantitative gas chromatographic—mass spectrometric assay has been developed for the determination of ethambutol (EMB) in human plasma. Plasma samples were taken from a patient after oral administration of EMB (with proven tuberculosis infection). Deuterated EMB and a non-deuterated analogue of EMB were synthesized and used as internal standards in this procedure; both gave excellent agreement in the analysis. The derivatizing agent used was trifluoroacetic anhydride (TFAA) and quantitative derivatization was complete in one hour, forming EMB-(TFA). Selective ion monitoring was utilized to monitor the gas chromatographic effluent. Ions were generated by electron impact at 70 eV. The limit of detection was 36 ng EMB per ml plasma. This method is compared with the electron-capture gas chromatographic procedure of Lee and Benet.

Clofazimine is useful in the treatment of Hansen's disease (leprosy) and some dermatological disorders, and is currently being used in drug regimens for patients with human immunodeficiency viral infections who are also infected with Mycobacterium avium complex. After an oral dose, absorption is variable, but when given in an oil-wax suspension is approximately 70%. Administration with food appears to increase the peak plasma drug concentration and reduce the time to peak level. Data on the volume of distribution and percentage or type of protein binding are not available; however, the drug undergoes extensive tissue distribution. Clofazimine does not cross the blood-brain barrier, but does cross the placenta, and is found in human breast milk. To date 3 urinary metabolites have been identified in man, but their biological activity is unknown. A substantial portion of the unchanged drug is excreted in faeces. The elimination half-life is variable, with values as long as 70 days being quoted in the literature. Frequently reported side effects of clofazimine are hyperpigmentation of the skin and conjunctiva, and abdominal pain. These resolve upon cessation of therapy. Biochemical and haematological adverse effects have been reported, but are generally not clinically relevant. Pharmacokinetic drug interactions of potential clinical significance have been observed with dapsone, oestrogen, rifampicin and vitamin A.

Information concerning passage of the antituberculosis drugs across the human placenta is sparse and scattered throughout the medical literature. Little mention was made of this subject in recent reviews of the clinical pharmacokinetics of these agents (Holdiness 1984, 1985a). However, a detailed survey indicates 6 of the 12 compounds commonly used have documented transplacental passage in humans (table I). If pregnancy occurs during the treatment of tuberculosis, the risk to the developing fetus must be considered in advising the expectant mother and her obstetrician. The indications for chemotherapy and the basic principles of management of the pregnant women with active tuberculosis are essentially no different from those in the non-pregnant patient (Snider 1984). Therapy with 2 drugs is instituted at standard doses, and the duration of treatment should not be altered by the patient's pregnancy. Retrospective studies by Snider et al. (1980) have revealed a reasonable margin of safety for isoniazid, rifampicin, and ethambutol when utilised during pregnancy; questionable results have precluded the administration of streptomycin. From their research of the literature, these authors showed that 94% of all gestations terminated in delivery of apparently normal term infants. In utero exposure of fetuses to antituberculosis therapy revealed 2.8% with classified birth defects. It was suggested that with the exception of women on streptomycin, the risk of adverse gestational outcomes is no greater among pregnant women on antituberculosis regimens than among healthy pregnant females. Caution must be exercised when considering the teratogenic effects of these drugs as spontaneous abortions, stillbirths, birth defects and prematurity are common even in normal pregnancy. The possible teratogenic effects of this class of antibiotics in animal models and humans have recently been reviewed (Holdiness 1987a) and the reader is referred to this article. Snider (1984) indicated that preventive therapy should be given during the second and third trimesters of pregnancy to selected patients at high risk of development of progressive disease. Treatment should be instituted promptly when a tuberculous infection is detected. Preferred regimens are isoniazid-ethambutol, isoniazid-rifampicin, or isoniazid-ethambutol-rifampicin, although other drugs may be needed if the disease is recurrent or if there is resistance to these primary drugs.

The literature has been reviewed for iatrogenic nutritional deficiencies induced by antituberculosis drugs. Of the 12 known compounds, 6 (isoniazid, rifampicin, pyrazinamide, para-aminosalicylic acid, kanamycin and cycloserine) have been documented to cause such abnormalities following human consumption. In most instances, the deficiencies were corrected by discontinuation of the offending agent; however, some individuals may require nutritional supplementation to achieve normal status. In susceptible persons, changes can be made in the diet or the antituberculosis regimen can be rearranged in order to allow both for appropriate management of the bacterial infection and adequate nutritional intake.

A quantitative gas chromatographic-mass spectrometric assay was developed for the determination of dopamine in subregions of rat brain. Five tissue punches weighing approximately 1.7 mg each were taken from the nucleus accumbens and four neostriatal regions differing in anterior-posterior level. The dopamine extracted from the tissue was treated with pentafluoropropionic anhydride (PFP) and quantitatively formed dopamine-(PFP)3. The derivatizing procedure took 15 min and the retention time for dopamine-(PFP)3 and its deuterated analogue [1,1,2,2-2H4]dopamine-(PFP)3) was 120 sec. Selective ion monitoring was utilized to monitor the gas chromatographic effluent. Ions were generated by electron impact ionization. The assay was able to measure concentrations of 1 nanogram dopamine per milligram protein. An anterior-posterior gradient of dopamine was observed in the striatum. This assay should be useful in studies examining the effects of experimental manipulations on dopamine content in relatively small areas of brain tissue.

The literature is reviewed for contact dermatitis associated with transdermal therapeutic systems. Clonidine, nitroglycerin, scopolamine, estradiol and testosterone are utilized in such applications, and fentanyl is under investigation. Most cutaneous reactions are limited to localized dermatitis; however, generalized systemic effects may occur. Investigators are reporting skin-related side-effects in up to 50% of patients using transdermal clonidine; however, with the other agents, this is demonstrated much less frequently. Reactivation of the dermatitis via oral medication, following sensitization to the patch, is noted in rare instances.

A fully portable, small-format X-ray imaging system, Lixiscope (low intensity X-ray imaging scope) is described. In the prototype, which has been built to demonstrate the feasibility of the Lixiscope concept, only well-developed and available components have been used. Consideration is given to the principles of operation of the device, some of its performance characteristics as well as possible dental, medical and industrial applications.

To the Editor. —In the April issue of theArchives, O'Donohue et al 1 presented an interesting article concerning pulmonary infection due to Mycobacterium bovis , and the use of short-term chemotherapy for treatment. I would like to comment on pharmacological therapy for such infection, especially in patients with possible liver disease. In an earlier letter in theArchives, 2 I discussed some of the causes of spread of this bacillus in humans. Historically, it is interesting to note that in 1917, 5% of the cattle in the United States were estimated to be infected with this strain, and approximately 25% of the deaths from tuberculosis in adult humans were actually caused by M bovis . Institution of surveillance programs and compulsory pasteurization of milk led to a dramatic decrease in human infection. However, infection still occurs, and a recent authoritative review of this subject suggested that once cases due to reactivation

To the Editor. —In their recent article, Baciewicz et al 1 presented an excellent update on rifampin drug interactions. There are, however, two therapeutic agents (ethionamide and protionamide) not mentioned that may have serious to potentially fatal consequences when used with rifampin. Ethionamide (α-ethylthioisonicotinamide) is a derivative of isonicotinic acid, and protionamide is the N -propyl derivative of ethionamide. These thioamides are used as "second-line" antituberculosis agents and are also used for the treatment of leprosy. It has been previously observed that simultaneous administration of rifampin and protionamide did not result in alteration of the pharmacokinetic properties of these antibiotics. 2 Regardless, clinically important interactions have been documented. Pattyn et al 3 noted hepatitis, mostly with jaundice, in 4.5% of 596 multibacillary leprosy patients treated daily for six months with a regimen of rifampin (600 mg), ethionamide (500 mg), and dapsone (100 mg). Mortality from this subgroup of individuals with

To the Editor. —In the MarchArchives, Snider and Powell1presented a well-organized review of the sparse and scattered data available in the literature concerning the appearance of antituberculosis drugs in human breast milk. The information available to these authors indicated thatp-aminosalicylic acid and pyrazinamide were either not detectable or unknown at the time of publication; however, my laboratory has recently analyzed both of these components in human breast milk. A 27-year-old woman (non-breast-feeding) was given 4 g ofp-aminosalicylic acid and breast milk collected at 0, 1, 2, 3, 4, 9, and 12 hours following oral administration. A maximum concentration of 1.1 mg/L was obtained at three hours with an elimination halflife of 2.5 hours. The maximum plasma concentration of the mother at two hours was determined to be 70.1 mg/L. Gastrointestinal tract irritation later developed and thep-aminosalicylic acid was withdrawn from the