We recovered a newly recognized spirochete from the blood, skin lesions (erythema chronicum migrans [ECM]), or cerebrospinal fluid of 3 of 56 patients with Lyme disease and from 21 of 110 nymphal or adult lxodes dammini ticks in Connecticut. These isolates and the original one from l. dammini appeared to have the same morphologic and immunologic features. In patients, specific IgM antibody titers usually reached a peak between the third and sixth week after the onset of disease; specific IgG antibody titers rose slowly and were generally highest months later when arthritis was present. Among 40 patients who had early disease only (ECM alone), 90 per cent had an elevated IgM titer (greater than or equal to 1:128) between the ECM phase and convalescence. Among 95 patients with later manifestations (involvement of the nervous system, heart, or joints), 94 per cent had elevated titers of IgG (greater than or equal to 1:128). In contrast, none of 80 control subjects had elevated IgG titers, and only three control patients with infectious mononucleosis had elevated IgM titers. We conclude that the I. dammini spirochete is the causative agent of Lyme disease.

In a randomized controlled trial of amphotericin B-based therapy for human immunodeficiency virus (HIV)-associated cryptococcal meningitis in Thailand, we also compared the mycological efficacy, toxicity, and pharmacokinetics of oral versus intravenous flucytosine at 100 mg/kg of body weight/day for the initial 2 weeks. Half of 32 patients assigned to the two arms containing flucytosine were randomized to oral and half to intravenous flucytosine. Early fungicidal activity was determined from serial quantitative cultures of cerebrospinal fluid (CSF), and toxicity was assessed by clinical and laboratory monitoring. Flucytosine and fluorouracil concentrations in plasma and CSF were measured by high-performance liquid chromatography. No significant bone marrow or hepatotoxicity was seen, there was no detectable difference in bone marrow toxicity between patients on intravenous and those on oral formulation, and no patients discontinued treatment. In patients receiving intravenous flucytosine, the median 24-h area under the concentration-time curve was significantly higher than in the oral group. Despite this difference, there was no difference in early fungicidal activity between patients on intravenous compared with patients on oral flucytosine. The results suggest that either formulation can be used safely at this dosage in a developing country setting, without drug concentration monitoring. The bioavailability of the oral formulation may be reduced in late-stage HIV-infected patients in Thailand. Concentrations of flucytosine with intravenous formulation at 100 mg/kg/day may be in excess of those required for maximal fungicidal activity.Flucytosine (5FC) in combination with amphotericin B (AMB) is standard therapy for cryptococcal meningitis in the United States and Europe. 5FC is taken up by fungal cells by cytosine permease and converted into fluorouracil (5FU) by fungal cytosine deaminase. Further metabolism of 5FU leads to the formation of 5-fluorouridine triphosphate, which is incorporated into fungal RNA, and 5-fluorodeoxyuridine monophosphate, an inhibitor of thymidylate synthetase. This results in inhibition of protein and DNA synthesis in the fungal cell (19).Side effects of 5FC include nausea, vomiting, diarrhea, bone marrow depression, and hepatotoxicity. The latter two are thought to be due to effects of 5FU. Human cells lack the enzyme cytosine deaminase and are unable to convert 5FC into 5FU. However, the human intestinal microflora has been shown to be capable of converting 5FC into 5FU in vitro (8, 10, 17), and 5FU, at concentrations known to be associated with bone marrow depression, has been measured in the plasma of patients treated with oral 5FC (6). If intestinal bacteria do play a role in conversion of 5FC to 5FU in patients, then oral administration of 5FC might be associated with increased 5FU concentrations and more side effects than intravenous (i.v.) administration of the drug. On the other hand, i.v. 5FC is more costly to administer in resource-poor settings and carries the added incon...

In the testes of sexually active grey squirrels 8 stages of spermatogenesis were recognized each with a characteristic association of germ cells. The low numbers of spermatozoa in squirrel testes are the result of fewer spermatogonial divisions compared with those of most other mammals as well as a low efficiency of spermatogenesis, with only 42% of the germ cells becoming spermatozoa. A period of testicular regression which may be prolonged follows the breeding season in June/July. In fully regressed testes no stages of spermatogenesis could be recognized, the lumen of the seminiferous tubules was occluded and no stages later than primary spermatocytes were seen.

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