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Biomedical subjects

J M Leonard

Publications and source records attributed to J M Leonard.

At least 55 records · Page 3Linked to original sources
PubMed1990

Tuberculous meningitis.

Tuberculous meningitis is an uncommon but potentially devastating form of tuberculosis. Current antituberculous drugs are highly effective when treatment is initiated early, before the onset of altered mentation or focal neurologic deficits. Because the clinical outcome depends greatly on the stage at which therapy is initiated, early recognition is of paramount importance. Patients with the meningoencephalitis syndrome and CSF findings of low glucose levels, elevated protein levels, and pleocytosis should be treated immediately if there is evidence of TB elsewhere in the body, or if prompt evaluation fails to establish an alternative diagnosis. Examination of CSF is the best diagnostic approach; with sufficient diligence, serial AFB smears and cultures will usually yield positive results, even days after therapy has been started. The CT scan is an important and highly effective tool for the diagnosis and management of patients with TBM. In a patient with compatible clinical features, the combination of basilar meningeal enhancement and any degree of hydrocephalus is strongly suggestive of the diagnosis of TBM. Serial evaluation by CT scanning is useful for following the course of hydrocephalus and tuberculoma, particularly in reference to the need for, or response to, adjunctive therapy with corticosteroids and surgery. The decision to administer corticosteroids should be based on careful correlation of the clinical and radiographic features of the case. Surgical shunting should be considered early in the patient with hydrocephalus and symptoms of raised intracranial pressure. Tuberculomas are best treated medically, often in conjunction with corticosteroids where cerebral edema is believed to contribute to neurologic decline. The recommended chemotherapy regimen is isoniazid and rifampin in all patients, together with pyrazinamide for the first 2 months.

Arachnoiditis↗
PubMed1988

Development of disease and virus recovery in transgenic mice containing HIV proviral DNA.

Transgenic mice containing intact copies of the human immunodeficiency virus (HIV) proviral DNA were constructed. Founder animals were not viremic for HIV and remained healthy during a 9-month observation period. After being mated with nontransgenic animals, one founder mouse (No. 13) gave rise to F1 progeny that developed a disease syndrome characterized by marked epidermal hyperplasia, lymphadenopathy, splenomegaly, pulmonary lymphoid infiltrates, growth retardation, and death by day 25 of life. Infectious HIV, indistinguishable from parental virus by immunoblot analysis, was recovered from the spleen, lymph nodes, and skin of five of five affected animals.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Cerebrospinal fluid formula in patients with central nervous system infection.

Knowledge of the CSF formula is clinically useful and at times critical in the analysis of a number of diagnostic problems presented by patients with CNS infections. The decision to withhold antimicrobial therapy in the patient with an acute meningitis syndrome, when viral etiology is suspected, is justified in the presence of a polymorphonuclear cellular reaction provided the CSF glucose is greater than 45 mg per dl and the protein less than 130 mg per dl. Patients who fail to improve clinically should be retapped in 8 to 12 hours. A persisting PMN reaction or the combination of a PMN pleocytosis and hypoglycorrachia virtually rules out viral infection and, in the face of negative routine cultures, requires a diligent search for focal parameningeal suppuration and consideration of CNS tuberculosis and fungal infection. Careful re-evaluation of the patient emphasizing factors such as duration of illness and potential sites of parameningeal suppuration will be useful in guiding further diagnostic studies. Head CT scanning including views of the sphenoid sinuses may be especially helpful in this regard.

Aged↗
PubMed1985

Male hypogonadotropic hypogonadism: factors influencing response to human chorionic gonadotropin and human menopausal gonadotropin, including prior exogenous androgens.

Although testosterone (T) therapy is sufficient for maturation and maintenance of secondary sex characteristics in hypogonadal men, gonadotropins are required for stimulation of spermatogenesis. Thirteen men with hypogonadotropic hypogonadism received treatment with hCG, followed in 12 by the addition of human menopausal gonadotropin (hMG). All initially had undetectable serum LH and FSH and low T levels and were azoospermic with small testes. During therapy, all achieved normal male levels of T. Twelve of 13 had marked and continuous increase in testicular volume. Three men had sperm in the ejaculate with hCG treatment alone. All but 1 patient developed sperm in their seminal fluid during combined hCG and hMG therapy. Two men achieved three pregnancies, and 2 more had semen that produced hamster oocyte penetration assays in the fertile range during the protocol period. Four of 5 who achieved sperm densities greater than 1 million/ml while receiving combined therapy maintained or increased sperm production while receiving continued hCG therapy after hMG was withdrawn. We examined the response to gonadotropin therapy of men who had received previous T therapy and those who had not. There were no differences in rapidity or degree of response, as assessed by rise in serum T, increase in testis volume, or maximal sperm density achieved. Multiple pituitary deficits and cryptorchidism were negative prognostic factors. In summary, the prognosis for successful stimulation of spermatogenesis in men with hypogonadotropic hypogonadism treated with hCG/hMG is good and not adversely affected by prior androgen treatment. Despite undetectable serum FSH levels, hCG treatment was sufficient to both initiate and maintain spermatogenesis in some patients.

Adult↗
PubMed1983

Late effects on gonadal function of cyclophosphamide, total-body irradiation, and marrow transplantation.

One hundred thirty-seven patients had gonadal function evaluated 1-11 years after marrow transplantation. All 15 women less than age 26 and three of nine older than age 26 who were treated with 200 mg/kg cyclophosphamide recovered normal gonadotropin levels and menstruation. Five have had five pregnancies resulting in three live births, one spontaneous abortion, and one elective abortion. Three of 38 women who were prepared with 120 mg/kg cyclophosphamide and 920-1200 rad total-body irradiation had normal gonadotropin levels and menstruation. Two had pregnancies resulting in one spontaneous and one elective abortion. Of 31 men prepared with 200 mg/kg cyclophosphamide, 30 had normal luteinizing hormone levels, 20 had normal follicle-stimulating hormone levels, and 10 of 15 had spermatogenesis. Four have fathered five normal children. Thirty-six of 41 men prepared with 120 mg/kg cyclophosphamide and 920-1750 rad total-body irradiation had normal luteinizing hormone levels, ten had normal follicle-stimulating hormone levels, and 2 of 32 studied had spermatogenesis. One has fathered two normal children. It was concluded that cyclophosphamide does not prevent return of normal gonadal function in younger women and in most men. Total-body irradiation prevents return of normal gonadal function in the majority of patients.

Acute Disease↗
PubMed1983

Sex hormone-binding globulin changes with androgen replacement.

Since sex hormone-binding globulin (SHBG) levels are often elevated in sera of patients with testicular insufficiency, it is important to determine whether SHBG declines into the normal range and the extent of change in free testosterone (free T) after androgen administration. Five normal men and five patients with Klinefelter's syndrome were studied before and after the administration of testosterone enanthate (200 mg, im every 2 weeks). An additional five normal men and five patients with hypogonadotropic hypogonadism (HH) were treated with hCG (2000 U, three times a week). Three months after the administration of T or hCG, serum total and free T increased in both normal men and patients. Free T increased significantly in the Klinefelter's and HH patients from 94 +/- 20 and 14 +/- 5 pg/ml, respectively, to 271 +/- 50 and 276 +/- 41 pg/ml (P less than 0.01; P less than 0.001). The increase in the normal men treated with T or hCG was also significant (from 211 +/- 52 and 220 +/- 37 pg/ml to 390 +/- 83 and 330 +/- 90 pg/ml). SHBG fell in both the T-treated normal men (from 6.5 +/- 1.2 ng dihydrotestosterone bound/ml to 4.3 +/- 0.4; P less than 0.02) and the T-treated Klinefelter's patients (from 16.4 +/- 2 to 4.3 +/- 0.5; P less than 0.01). However, it was unchanged in the hCG-treated HH patients and rose in the hCG-treated normal men (from 6.6 +/- 0.7 to 8.6 +/- 1.0; P less than 0.05). This study demonstrates that treatment of hypogonadal men with T and hCG in the doses used increased free T levels above the basal levels for normal men. However, the effects of the increase in free T, as determined by a change in SHBG, were different depending upon the type of treatment.

Adult↗
PubMed1982

Continuous RBC transfusions in a patient with sickle cell disease.

A patient with severe sickle cell anemia received approximately 600 RBC transfusions during a period of 30 years. Continuous prophylactic transfusions were administered for 13 years. During the 13-year period, except for tissue damage already inflicted by sickle cell disease, she was free of symptoms. When a hemoglobin concentration of 12 g/dL was maintained, she was shown to have ineffective erythropoiesis postulated to be due to the inability of her reticulocytes to cross the sinusoidal barrier from marrow to blood. Up to the time of her death at the age of 47 years, there was no evidence that her massive iron overload produced clinical symptoms other than unexplained, although her massive iron overload remains suspect.

Anemia, Sickle Cell↗
PubMed1980

Phosphatidic acid accumulation in the membranes of Escherichia coli mutants defective in CDP-diglyceride synthetase.

CTP-phosphatidic acid cytidylyltransferase (CDP-diglyceride synthetase) is a key enzyme in the biogenesis of membrane phospholipids in Escherichia coli. Using a modification of a previously described autoradiographic screening procedure (Raetz, C. R. H. (1975) Proc. Natl. Acad. Sci. U.S.A. 72, 2274-2278), we have isolated six mutant strains in which the specific activity of the synthetase is 1 to 10% that of the wild type, as judged by in vitro assays. The synthesis of dCDP-diglyceride, as well as CDP-diglyceride, is defective in these organisms. The mutations responsible for the enzyme defects (designated cds) all map in the same location near minute 4 on the chromosome. Although none of the mutants obtained are temperature-sensitive for growth, all of them exhibit significantly elevated levels of phosphatidic acid in vivo. The highest increase is observed in the mutant GL60, in which phosphatidic acid constitutes about 5% of the membrane lipid, in contrast to 0.2% in typical wild type strains. The accumulation of phosphatidic acid occurs primarily at the expense of phosphatidylglycerol and cardiolipin, but the total lipid-to-protein ratio of GL60 is nearly normal. In vivo labeling of GL60 with 32Pi suggests that the increased phosphatidic acid pool is the result of a partial metabolic block early in the phospholipid pathway, but that most of this expanded pool is nonetheless available for de novo synthesis.

Cell Membrane↗
PubMed1980

Psoriasis, methotrexate, and oligospermia.

A young man with severe psoriasis was treated intermittently with methotrexate. On two different occasions, severe oligospermia documented by serial seminal fluid analyses was present coincident with methotrexate administration. Discontinuation of methotrexate resulted in normal sperm concentration. Measurements of serum gonadotrophin and testosterone levels were normal during and after methotrexate treatment. It is concluded that methotrexate administration may result in severe oligospermia and that these inhibiting effects on spermatogenesis are reversible.

Adult↗
PubMed1980

Effects of conceptual task difficulty on generalized persistence.

A set of experiments tested whether the degree of effort rewarded in a conceptual task would affect subsequent persistence in a perceptual task. College students were presented with complex, simple, or unsolvable anagrams or, in a control group, merely read the anagram target words; the perceptual task requiring the identification of subtle or nonexistent differences between cartoon drawings followed. Those who had worked on unsolvable anagrams spent greater time on the cartoon drawings compared with those who had worked on simple anagrams or anagram target words, suggesting that initial failure on assigned tasks serves as a cue to work harder. The complex group spent more time on the cartoon task than the simple group, control group and, following sufficient failure, the unsolvable group. The complex group was also found to spend more time on the cartoons than a group which experienced exactly the same distribution of successes and failures on the anagrams but which always failed after high effort. Two interpretations of the superior persistence of the complex group were compared: (a) the degree of accustomed effort per reinforcer becomes a generalized component of instrumental behavior, and (b) high effort increases the habituation of frustration-produced disruptive responses.

Concept Formation↗
PubMed1979

Allogeneic marrow grafting for acute leukemia: a follow-up of long-term survivors.

We have reported 100 consecutive patients with refractory acute leukemia treated with chemotherapy, total body irradiation (TBI) and marrow from an HLA identical sibling. At the time of the report 17 patients were alive after 11-53 months. All patients have now been followed more than 3 years. At the time of the last report 4 of the 17 patients had relapsed: two in the marrow, one in the central nervous system and one in the testicle. Three of these four patients have died of their disease 27, 34 and 50 months following transplant. The patient with a solitary testicular relapse remains in complete remission 49 months after local irradiation without concomitant systemic therapy. One other patient died 26 months following transplantation from cardiopulmonary complications following multiple respiratory infections. Of the 13 surviving patients, three suffer from chronic graft-versus-host disease. Summaries of the problems encountered in these patients after the first 100 days are presented. Ten of the original 100 patients are living productive lives 36-80 months after transplantation. The data clearly demonstrate that long-term unmaintained remissions are possible in a small fraction of patients with terminal leukemia treated with various chemotherapy regimens and TBI followed by marrow transplantation.

Adolescent↗
PubMed1978

True prostatic tissue in 46,XX female with adrenogenital syndrome.

A case is presented of a seventeen-year-old phenotypic male with empty scrotum, hormonal studies consistent with adrenogenital syndrome, a 46,XX karyotype, and a normal prostate on rectal examination. Histochemical evidence of the true nature of the prostatic tissue is presented, and the developmental aspects of the case are discussed.

Adolescent↗
PubMed1978

Gentamicin-resistant bacillary infection. Clinical features and amikacin therapy.

Infections caused by gentamicin sulfate-resistant Pseudomonas aeruginosa and Serratia marcescens have occurred in multiple areas of our hospitals and have caused serious clinical illness and death. Isolates of Pseudomonas organisms were sensitive to some alternative drugs including collstin sulfate, but isolates of Serratia organisms were often resistant to all commercially available parenteral antimicrobiais. All isolates were inhibited by amikacin sulfate, and 95% were killed by concentrations achievable in serum with recommended doses. Twenty patients with hospital-acquired infections, including ten with septicemia, were treated with amikacin. Eighteen of the 20 patients had a good clinical and bacteriologic response. Ototoxicity and nephrotoxicity each occurred in one patient.

Adult↗
PubMed1976

The role of varicocele in male fertility.

In summary, seventeen infertile men with varicocele in whom no other cause for infertility could be identified, were studied before and following varicocele repair. Morphologic alterations were the most common abnormality noted in the seminal fluid with all subjects demonstrating increased numbers of tapered or amorphous spermatozoa. Ligation of the varicocele resulted in improvement in one or more of the seminal fluid abnormalities in thirteen of the seventeen patients. Seven patients achieved a pregnancy. No single seminal fluid parameter was identified which was of predictive value in determining those subjects who would demonstrate improvement following varicocele repair.

Adult↗