The association between maternal cocaine use and placenta previa

We compared various diagnostic tests for their abilities to detect Mycobacterium ulcerans infection in specimens from patients with clinically active disease. Specimens from 10 patients from the area of Zangnanado (Department of Zou, Benin) with advanced, ulcerated active M. ulcerans infections were studied by direct smear, histopathology, culture, PCR, and oligonucleotide-specific capture plate hybridization (OSCPH). A total of 27 specimens, including 12 swabs of exudate collected before debridement and 15 fragments of tissue obtained during debridement, were submitted to bacteriologic and histopathologic analysis. The histopathologic evaluation of tissues from all six patients so tested revealed changes typical of those caused by M. ulcerans infection. Five specimens were contaminated, and M. ulcerans was cultivated on L?wenstein-Jensen medium from 12 of the remaining 22 (54.5%) specimens. Detection of mycobacteria was performed by PCR, and M. ulcerans was detected by OSCPH with a new probe (5'-CACGGGATTCATGTCCTGT-3') reacting with M. ulcerans and Mycobacterium marinum. In 10 of 22 (45.5%) specimens, M. ulcerans was identified by PCR-OSCPH. There was no statistically significant difference between the detection of M. ulcerans by culture and by PCR-OSCPH (P > 0.05). This is the first demonstration of an amplification system (PCR-OSCPH) with a sensitivity similar to that of culture for the direct and rapid recognition of M. ulcerans in clinical specimens. This system is capable of identifying M. ulcerans, even in paucibacillary lesions. Our findings suggest that PCR-OSCPH should be used in the quest for the elusive environmental reservoir(s) of M. ulcerans.     

Experimental alimentary infection of anole lizards (Anolis carolinensis) with Mycobacterium ulcerans

Pathogenic Mycobacterium ulcerans were recovered from the stool of anole lizards up to 11 days after inoculation by stomach tube. M. ulcerans was isolated from the liver of 3 of 20 lizards and acid fast bacteria were seen in the mucosa of intrahepatic bile ducts in 2 of these 10 weeks post-inoculation. These results provide equivocal support for our hypothesis that herpetofauna are a reservoir of infection with M. ulcerans.     

Detection of Mycobacterium ulcerans in environmental samples during an outbreak of ulcerative disease

Mycobacterium ulcerans is an environmental bacterium which causes chronic skin ulcers. Despite significant epidemiological evidence to suggest that water is the source of infection, the organism has never been identified in the environment. Environmental water samples were collected from a small town in which an outbreak of 29 cases had occurred in a 3-year period. These were examined by mycobacterial culture and PCR amplification. Similar to previous studies, M. ulcerans was not cultured from the water samples. However, five samples were positive for M. ulcerans by PCR. These samples were collected from a swamp and a golf course irrigation system within the outbreak area. This is the first time that M. ulcerans has been demonstrated to be present in the environment and supports the postulated epidemiology of disease due to this organism.     

Red-back spider bites to Perth children, 1979-1988

The aim of this study was to describe the pattern of illness caused by red-back spider bites to children in Perth, Western Australia, over a 10 year period, and to compare it with that in adults. The case-notes of 241 (89%) of the 271 children admitted to Princess Margaret Hospital and Fremantle Hospital with suspected red-back spider bite from 1979 to 1988 were available for analysis. A definite bite was defined as a definite bite by a positively identified red-back spider, positive identification of a red-back spider with no definite bite but the later development of typical symptoms or no definite history of red-back spider bite but strong clinical evidence and complete recovery after administration of antivenom. Systemic envenomation was accepted if there were symptoms of vomiting, generalized pain or sweating, or abdominal pain. Sixty-five per cent of children were definitely bitten. As found in previous adult and mixed studies, there was a peak incidence in the warmer months with a male preponderance (68%); 81% of bites were to the extremities and 83% of bites occurred in the daytime. The syndrome produced in children was usually similar to that seen in adults. Twenty-one per cent of children received antivenom, a rate comparable to previous studies in older age groups; however, no child received more than one ampoule. Compared with data extracted from a previously published study at Fremantle Hospital, in which 37% of adults treated with antivenom received more than one ampoule, these findings suggest that contrary to current opinion children may not be at an increased risk of morbidity from latrodectism.     

Mycoplasma hyopneumoniae potentiation of porcine reproductive and respiratory syndrome virus-induced pneumonia

An experimental model that demonstrates a mycoplasma species acting to potentiate a viral pneumonia was developed. Mycoplasma hyopneumoniae, which produces a chronic, lymphohistiocytic bronchopneumonia in pigs, was found to potentiate the severity and the duration of a virus-induced pneumonia in pigs. Pigs were inoculated with M. hyopneumoniae 21 days prior to, simultaneously with, or 10 days after inoculation with porcine reproductive and respiratory syndrome virus (PRRSV), which induces an acute interstitial pneumonia in pigs. PRRSV-induced clinical respiratory disease and macroscopic and microscopic pneumonic lesions were more severe and persistent in M. hyopneumoniae-infected pigs. At 28 or 38 days after PRRSV inoculation, M. hyopneumoniae-infected pigs still exhibited lesions typical of PRRSV-induced pneumonia, whereas the lungs of pigs which had received only PRRSV were essentially normal. On the basis of macroscopic lung lesions, it appears that PRRSV infection did not influence the severity of M. hyopneumoniae infection, although microscopic lesions typical of M. hyopneumoniae were more severe in PRRSV-infected pigs. These results indicate that M. hyopneumoniae infection potentiates PRRSV-induced disease and lesions. Most importantly, M. hyopneumoniae-infected pigs with minimal to nondetectable mycoplasmal pneumonia lesions manifested significantly increased PRRSV-induced pneumonia lesions compared to pigs infected with PRRSV only. This discovery is important with respect to the control of respiratory disease in pigs and has implications in elucidating the potential contribution of mycoplasmas in the pathogenesis of viral infections of other species, including humans.     

Lyme disease in children and adolescents

148 children and adolescents with Lyme borreliosis and tick bite or suspection on tick bite were examined. The examined patients were aged from 14 months to 24 years and divided into four age groups. Skin lesions were discovered in 25 percent of patients with tick bite. Erythema migrans occurred in 91 percent, Lymphocytoma in 3 percent and sclerodermatous lesions (Lichen sclerosus et atrophicus and Morphea) in 6 percent of patients with Lyme disease. Serologic tests on the presence of antibodies to Borreliae burgdorferi were performed in 96 percent of cases with tick bite. Antibody titer 1:80 or higher in 8 percent of patients with tick bite, was discovered. We found positive serologic test results in 5 (29 percent) of 29 persons with Erythema migrans, in 4 (4 percent) of 110 patients with tick bite (without skin lesions), as well as, in 1 patient with Lymphocytoma. Antibiotic therapy was applied in all cases with Erythema migrans, in person with Lymphocytoma, as well as, in patients with asymptomatic infections (patients without skin lesion recalling a tick bite and with antibodies against Borrelia burgdorferi). A general sensitivity, to infection with Borrelia burgdorferi, is stressed, a fact based on appearance by Lyme borreliosis in all age groups even in the newborn children.     

Pathogenicity of Mycoplasma synoviae in broiler chickens

Six isolates of Mycoplasma synoviae, identified as WVU 1853, K1968, K1858, 92D8034, F10-2AS, and FMT, were compared for pathogenicity in broiler chickens. Specific-pathogen-free chickens were inoculated, in two groups of 20, with each isolate by footpad or eyedrop inoculation at 1 day of age and were examined at necropsy 7, 14, 28, and 42 days postinoculation. Specimens were taken for histopathology, culture, polymerase chain reaction assay, and hemagglutination-inhibition serology. Isolates were grouped according to pathogenicity on the basis of differences in lesion development and tissue distribution in the respiratory system, other viscera, and the skeletal system. K1968 (pathogenic) induced lesions in all sites examined in both the footpad and eyedrop inoculation groups. It was detected in all sites following footpad inoculation and in all sites except viscera following eyedrop inoculation. WVU 1853, K1858, and 92D8034 (moderately pathogenic) induced lesions and were detected in all sites following footpad inoculation. With eyedrop inoculation, lesions were identified only in upper and lower respiratory sites, and organisms were detected only in upper respiratory sites. F10-2AS (moderately pathogenic) was similar; however, footpad inoculation failed to induce visceral lesions or permit organism detection in any site. F10-2AS was detected in upper and lower respiratory tissues following eyedrop inoculation. FMT (mildly pathogenic) induced only upper respiratory lesions when either footpad or eyedrop inoculation was used, and detection was restricted to upper respiratory sites following eyedrop inoculation. These results are useful in comparative evaluations of the virulence of other M. synoviae isolates and form a basis for characterization of virulence factors of M. synoviae.     

Differentiation of Mycobacterium ulcerans, M. marinum, and M. haemophilum: mapping of their relationships to M. tuberculosis by fatty acid profile analysis, DNA-DNA hybridization, and 16S rRNA gene sequence analysis

Although Mycobacterium ulcerans, M. marinum, and M. haemophilum are closely related, their exact taxonomic placements have not been determined. We performed gas chromatography of fatty acids and alcohols, as well as DNA-DNA hybridization and 16S rRNA gene sequence analysis, to clarify their relationships to each other and to M. tuberculosis. M. ulcerans and M. marinum were most closely related to one another, and each displayed very strong genetic affinities to M. tuberculosis; they are actually the two mycobacterial species outside the M. tuberculosis complex most closely related to M. tuberculosis. M. haemophilum was more distinct from M. ulcerans and M. marinum, and it appeared to be as related to these two species as to M. tuberculosis. These results are important with regard to the development of diagnostic and epidemiological tools such as species-specific DNA probes and PCR assays for M. ulcerans, M. marinum, and M. haemophilum. In addition, the finding that M. ulcerans and M. marinum are more closely related to M. tuberculosis than are other pathogenic mycobacterial species suggests that they may be evaluated as useful models for studying the pathogenesis of M. tuberculosis. M. marinum may be particularly useful in this regard since strains of this species grow much more rapidly than M. tuberculosis and yet can cause systemic disease in immunocompromised hosts.     

Development of an experimental model of Microsporum canis infection in cats

An experimental infection model was developed for reliable induction of Microsporum canis skin infections in cats, using a defined number of macroconidia harvested from the fungus in culture. The strain of M. canis used produced highly fluorescent hairs under ultraviolet illumination. Kittens 8 to 9 weeks of age (n = 6) received 10(5) macroconidia applied topically to a closely-shaved area of skin. Sites were dressed with an occlusive bandage for 3 days, then grooming was restricted for an additional 4 weeks. Lesions were first observed 2 weeks after inoculation, enlarged over the following 6 to 8 weeks, then decreased in size and appeared healed at 12 to 14 weeks after inoculation. Cats often developed satellite lesions on the face, ears, or other body regions. The experimental infections strongly resembled moderately severe cases of naturally-occurring feline dermatophytosis in clinical patients. This experimental infection model will be useful for evaluation of topical and systemic treatments for feline M. canis infection.     

Guided bone regeneration in dental implant treatment using a bioabsorbable membrane

1. Australia has some of the most venomous fauna in the world. Although humans are not usually perceived as being predators against these animals they are often envenomated, accidentally or otherwise. This has led to the development of antivenoms against some of the potentially lethal venoms. However, further understanding of the mechanism(s) of action of these and other venoms is important, not only for developing new treatment strategies but also in the search for novel research tools. 2. The present review discusses the pharmacology of some of the components found in venoms and outlines the research undertaken on some of Australia's venomous animals, with the exception of snakes. 3. Biogenic amines, peptides and enzymes are common venom components and produce a wide range of effects in envenomated humans. For example, respiratory failure observed after envenomation by the box jellyfish (Chirnex fleckeri) and Sydney funnel-web spider (Atrax robustus) is most likely due to potent neurotoxins in the venoms. Stonefish (Synanceja trachynis) and platypus (Ornithorhynchus anatinus) venoms, although not considered lethal, cause severe pain. However, the components responsible for these effects have not been isolated. Venom components, as yet unidentified, may be responsible for the cutaneous necrotic lesions that have been reported after some spider bites (e.g. Lampona cylindrata). Other venoms, such as those of the jumper ant (Myrmecia pilosula) and bull ant (M. pyriformis), may produce only mild skin irritation to the majority of humans but a severe anaphylactic response in sensitized victims. 4. While there has been a renewed interest in toxinology, further research is required to fully elucidate the pharmacological action of many of these venoms.     

Black widow spider (Latrodectus tredecimguttatus) bite. Presentation of 12 cases

The most severe cases of arachnidism are those due to Latrodectus tredecimguttatus spider-bite. The Mediterranean area is the habitat of the L. tredecimguttatus species. In the last few years no series of patients with latrodectism has been reported in Spain. A retrospective study of the patients admitted for L. tredecimguttatus spider bite in the Torrecárdenas Hospital in Almeria, Spain from 1984 to 1994 was performed. Twelve patients were diagnosed with latrodectism. Eleven were bitten while carrying out agricultural tasks, 8 of which were performed in greenhouses. The mean time between the bite and the appearance of the general symptoms was 40 minutes (20-120 minutes), with the most common signs and symptoms being: pain and abdominal stiffness (10 cases), erythema (10 cases) or pain (8 cases) at the site of the bite, thoracic pain, pain in extremities and contractures and psychomotor alterations (6 cases). Laboratory findings were limited to leukocytosis (4 cases), increase in creatinphosphokinase count (4 cases) and proteinuria (3 cases). All the patients received analgesics, 6 were administered myorelaxants and calcium gluconate was given in 6 cases. The evolution was good without complications in all of the patients. Latrodectism is a rare phenomenon Spain. The diagnosis is difficult when there is absence of a clear history of spider bite and due to the lack of knowledge as to its semiology. Antivenom serum is not usually required.     

Epidemiology of disease caused by nontuberculous mycobacteria

The clinically important nontuberculous mycobacteria include M. kansasii, M. genavense, M. marinum, M. simiae, M. scrofulaceum and M. szulgai, M. avium, M. haemophilum, M. intracellulare, M. malmoense, M. ulcerans, and M. xenopi, M. abscessus, M. chelonae, M. fortuitum, and (rarely) M. smegmatis. Four clinical syndromes account for nearly all cases: pulmonary disease, lymphadenitis, skin or soft tissue disease, and disseminated disease in AIDS. M. avium and M. intracellulare (known together as M. avium complex), are the most common causes of pulmonary disease, lymphadenitis, and disseminated disease. All four clinical syndromes seem to be increasing in frequency, particularly in immunosuppressed hosts. Nontuberculous mycobacteria are acquired from the environment, but specific reservoirs of these organisms leading to human disease have not been defined.     

A case of nonscarring inflammatory epidermolysis bullosa acquisita: characterization of IgG autoantibodies by immunofluorescence, immunoblotting and immunogold electron microscopy

We report a case of nonscarring inflammatory epidermolysis bullosa acquisita in a 59-year-old Japanese woman. She developed blisters and erosions on her lip, trunk and extremities. Sodium aurothiomalate was effective for the skin lesions. The patient had been free from bullous skin lesions for the last 13 years and had shown no scarring. Indirect immunofluorescence (IF) study on 1 M NaCl-split skin revealed IgG autoantibodies against the dermal side of the split skin. Immunoblotting using normal human dermal extracts disclosed IgG autoantibodies reactive with the 290 and 145 kD antigens. Circulating IgG autoantibodies were deposited on the lamina densa by immunoelectron microscopy. IF mapping using several antibodies for the components of the basement membrane zone revealed blister formation at the lamina densa. These results suggest that the cleavage at the lamina lucida does not necessarily exclude the diagnosis of EBA and that the definite diagnosis of EBA should be confirmed by immunoblotting or immunoelectron microscopic study.     

Cutaneous histopathology of Rocky Mountain spotted fever

The dermatologic diagnosis of Rocky Mountain spotted fever (RMSF) is often presumptive; the clinical presentation includes skin rash and febrile illness with or without a clear history of tick bite. The characteristic cutaneous manifestations include a generalized skin eruption with purpuric, blanching or non-blanching macules and papules usually involving the extremities. Although skin biopsies are often performed to confirm the diagnosis, the spectrum of cutaneous histopathology in RMSF has not been well described. We studied a series of 26 cases of RMSF, of which 10 were surgical specimens and 16 were autopsies. The microscopic changes were correlated with the duration of illness. The main histopathologic feature was lymphohistiocytic capillaritis and venulitis with extravasation of erythrocytes, edema, predominantly perivascular and some interstitial infiltrate. Leukocytoclastic vasculitis (LCV) with neutrophilic infiltrate and nuclear dust was seen in 11 of 15 (73%) specimens from involved skin. These lesions with LCV also showed notable epidermal change including basal layer vacuolar degeneration with mild dermoepidermal interface lymphocytic exocytosis. Six lesions with LCV displayed focal fibrin thrombi and capillary wall necrosis. Apoptotic keratinocytes were noted in 3 lesions with LCV. Subepidermal blister was observed in the skin lesion of an autopsied patient with LCV changes. Another lesion of a fatal case with LCV also contained features of acute neutrophilic eccrine hidradenitis. Focal small nerve twig inflammation was noted in a third autopsy case with LCV. Plasma cells were seen in 6 of 34 specimens (18%); and eosinophils were observed in 3 (9%). The subcutaneous fat contained a mild perivascular inflammation and one case revealed focal lobular neutrophilic inflammation. Immunohistologic (IH) staining using polyclonal rabbit anti-Rickettsia rickettsii demonstrated positive staining of the organisms in the affected endothelial cells in all 12 cases tested. The cutaneous histopathology of RMSF is caused by endothelial damage by the rickettsial organisms which elicit an initial lymphohistiocytic small vessel vasculitis with progression to LCV. The vasculitis in RMSF is, therefore, considered to be a form of septic vasculitis.     

Effect of reduced bronchial circulation on lung fluid flux after smoke inhalation in sheep

Murine monoclonal antibodies directed against proteins of Borrelia burgdorferi B31 (low passage) were generated by the administration of antigen via the bite of borrelia-infected ticks. This strategy was employed as a mechanism to create antibodies against antigens presented by the natural route of tick transmission versus those presented by inoculation with cultured borreliae. One of the resultant antibodies reacted with a 17-kDa antigen from cultured B. burgdorferi, as seen by immunoblot analysis. This antibody was used to screen a B. burgdorferi genomic DNA lambda vector expression library, and an immunoreactive clone was isolated. DNA sequence analysis of this clone, containing a 2.7-kb insert, revealed several open reading frames. These open reading frames were found to be homologs of genes discovered as a multicopy gene family in the 297 strain of B. burgdorferi by Porcella et al. (S. F. Porcella, T. G. Popova, D. R. Akins, M. Li, J. D. Radolf, and M. V. Norgard, J. Bacteriol. 178:3293-3307, 1996). By selectively subcloning genes found in this insert into an Escherichia coli plasmid expression vector, the observation was made that the rev gene product was the protein reactive with the 17-kDa-specific monoclonal antibody. The rev gene product was found to be expressed in low-passage, but not in high-passage, B. burgdorferi B31. Correspondingly, the rev gene was not present in strain B31 genomic DNA from cultures that had been passaged >50 times. Serum samples from Lyme disease patients demonstrated an antibody response against the Rev protein. The generation of an anti-Rev response in Lyme disease patients, and in mice by tick bite inoculation, provides evidence that the Rev protein is expressed and immunogenic during the course of natural transmission and infection.     

Latrodectism in a child

BACKGROUND: The malmignatte Latrodectus mactans tredecimguttatus, commonly known as a black widow spider, can be found in the Mediterranean region. Its bite is a cause of a rarely seen syndrome called latrodectism. CASE REPORT: During a visit to Corsica, a 13-year-old boy developed abrupt severe abdominal pain and spasmodic muscular contractions, headache and vomiting. The patient was restless and experienced hallucinations including distressing visions of death. His high blood pressure (154/100 mmHg) returned to normal within 3 days. Clinical examination revealed dyspnea and facial edema associated with blepharoconjunctivitis and hyperreflexia, together with a scattered erythema and pruritus. These changes took place within minutes, after a probable black widow spider bite. The abdominal and neuropsychiatric symptoms disappeared after 5 days. Treatment with calcium gluconate, paracetamol, phloroglucinol and hydroxyzine had no effect, but diazepam decreased the acuteness of the symptoms. Anti-venom serum was not used. CONCLUSION: Diagnosis of latrodectism must be based on clinical and epidemiological data. Erroneously diagnosing surgical acute abdomen, renal colic, meningitis, tetanus or opioid withdrawal would entail incorrect treatment.     

Kinetics of appearance of intestinal lesions in mice mono-associated with a lethal or non-lethal strain of Clostridium difficile

The kinetics of the appearance of intestinal lesions induced by orogastric inoculation of gnotobiotic mice with a lethal strain of Clostridium difficile (VPI) that produced toxins A and B in vivo and in vitro was studied and compared with the lesions induced by non-lethal C. difficile strain 786 that produced toxins A and B in vitro but only toxin B in measurable amounts in vivo. Different portions of the intestine were removed 12, 20, 26 and 30 h after inoculation and studied by scanning electronmicroscopy. The remaining portions were homogenised for enumeration of C. difficile and quantification of toxin A by enzyme immunoassay and toxin B by cytotoxicity. The results showed that, following inoculation: (i) measurable amounts of both toxins were necessary to produce lesions; (ii) with strain VPI, the caecum and the colon were rapidly impaired and completely destroyed after 1 day, whereas the small intestine was damaged to a lesser extent; (iii) C. difficile strain 786 did not cause mucosal damage but induced mucus-like or serum-like secretion and morphological changes in the caecal enterocytes only.     

Moloney murine leukemia virus infects cells of the developing hair follicle after neonatal subcutaneous inoculation in mice

The nature of Moloney murine leukemia virus (M-MuLV) infection after a subcutaneous (s.c.) inoculation was studied. We have previously shown that an enhancer variant of M-MuLV, Mo+PyF101 M-MuLV, is poorly leukemogenic when used to inoculate mice s.c., but not when inoculated intraperitoneally. This attenuation of leukemogenesis correlated with an inability of Mo+PyF101 M-MuLV to establish infection in the bone marrow of mice at early times postinfection. These results suggested that a cell type(s) is infected in the skin by wild-type but not Mo+PyF101 M-MuLV after s.c. inoculation and that this infection is important for the delivery of infection to the bone marrow, as well as for efficient leukemogenesis. To determine the nature of the cell types infected by M-MuLV and Mo+PyF101 M-MuLV in the skin after a s.c. inoculation, immunohistochemistry with an anti-M-MuLV CA antibody was performed. Cells of developing hair follicles, specifically cells of the outer root sheath (ORS), were extensively infected by M-MuLV after s.c. inoculation. The Mo+PyF101 M-MuLV variant also infected cells of the ORS but the level of infection was lower. By Western blot analysis, the level of infection in skin by Mo+PyF101 M-MuLV was approximately 4- to 10-fold less than that of wild-type M-MuLV. Similar results were seen when a mouse keratinocyte line was infected in vitro with both viruses. Cells of the ORS are a primary target of infection in vivo, since a replication defective M-MuLV-based vector expressing beta-galactosidase also infected these cells after a s.c. inoculation.     

Clinical picture and therapy of portal-systemic encephalopathy (author's transl)

The clinical syndrome of portal-systemic encephalopathy is caused by far advanced cirrhosis of the liver in most cases; it is characterized by increasing drowsiness, disturbances of mentation, flapping tremor and hyperreflexia. An early diagnosis can be established by testing writing and drawing abilities. Increased occurrence of spider nevi, a dry, deep red tongue, and hemorrhagic lesions of skin and mucous membranes are symptoms of incipient hepatic insufficiency. The syndrome is initiated in most cases by excessive intake of protein or alcohol, by intestinal bleeding, by diuretics, or by intercurrent infections. Therapy has to include elimination of causes, reduced intake of protein, enemas with acetate buffer solution and oral medication with lactulose, bifidum milk, and certain amino acids in order to lower hyperammoniemia; in serious cases neomycin has to be given. At the same time a normalization of fluid and electrolyte balance has to be achieved; replacement of potassium is especially important, when hypokalemia and alcalosis are present. In general prognosis of portal-systemic encephalopathy however is serious, depending primarily upon the fact, whether or not sufficient functional hepatic parenchyma is present.     

Activity of two doses of rifampin against Mycobacterium leprae

In the course of a clinical trial designed to re-examine the bactericidal efficiency of 600-mg doses of rifampin (RMP) against Mycobacterium leprae, two doses of RMP, either 600 mg or 1200 mg, were administered 28 days apart to 29 previously untreated patients with lepromatous or borderline leprosy. Seven, 28, and 35 days after the start of the trial, skin biopsies were performed and immunologically normal mice were inoculated with 5 x 10(3) or 10(4) M. leprae in each hind foot pad. The patients assigned to the two regimens did not differ significantly in terms of sex, age, disease classification, bacterial index, or the concentration of M. leprae in the skin lesion biopsied for the inoculation of mice. The concentrations of organisms in the skin-biopsy specimens did not change significantly over the course of the trial among the patients, whether they were being treated by the first or the second regimen. The M. leprae recovered from specimens obtained from 21 of the patients, before beginning treatment, multiplied in a majority of the mice inoculated. The results of mouse inoculation confirmed the rapid bactericidal effects of RMP against M. leprae: a single dose of RMP rendered the organisms obtained from all but two of the patients incapable of multiplying in mice. No significant difference was demonstrated between the two regimens, nor was an additional effect of the second dose of RMP observed.