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Biomedical subjects

J de Koning

Publications and source records attributed to J de Koning.

At least 73 records · Page 4Linked to original sources

Myositis caused by Borrelia burgdorferi: report of four cases.

Myositis was proven histopathologically in 4 patients (age range 36-66 years) who suffered from early or late stages of Borrelia burgdorferi infection. Muscle weakness was present in 3 patients, 1 complaining of additional myalgias. One man came to medical attention because of skin discoloration and swelling of one leg. Deep biopsy from skin, fascia and muscle revealed acrodermatitis chronica atrophicans, panniculitis, fasciitis, and myositis, respectively. Creatine kinase was slightly elevated in 3 cases and normal in one. Infiltrates were found in the perimysium and within the muscle bundles, mainly around small vessels. The infiltrates consisted of many B cells and T4 lymphocytes with fewer cytotoxic T cells, suggesting that Borrelia myositis might be due to a local immune response to unknown Borrelia antigens. Cultivation of Borrelia from muscle was not successful. Antibiotic therapy cured the myositis.

Adult↗

A malignant mixed gonadal stromal tumor of the testis with heterologous components and i(12p) in one of its metastases.

A malignant mixed gonadal stromal tumor with mesenchymal heterologous elements of the testis is presented. This entity has been described in the ovary, but not hitherto in the testis. Karyotyping and ploidy measurement was done of the primary tumor and of an inguinal and lung metastases. The DNA ploidy and modal chromosome numbers were in agreement with each other in all samples. The most significant cytogenetic finding was the presence of the metacentric germ cell tumor marker i(12p) in an inguinal metastasis. This marker has been demonstrated in testicular and ovarian germ cell tumors and in a mixed Müllerian tumor, which raises the question of a possible relationship between the pluripotency of these tumors and the presence of i(12p).

Chromosome Aberrations↗

Demonstration of spirochetes in cardiac biopsies of patients with Lyme disease.

Cardiac involvement occurring early in Borrelia burgdorferi infection is a clinical manifestation of human Lyme disease. Therefore, two patients with acute complete atrioventricular heart blocks and unexplained recurrent dizziness were studied. Both patients had significantly elevated serum titers of IgM and IgG antibodies to B. burgdorferi. Right ventricular subendocardial biopsies showed dense infiltrates consisting of lymphocytes and plasma cells. Silver staining revealed spirochetes characteristic of B. burgdorferi near and in the infiltrates, between the muscle fibers, and in the endocardium. One patient responded to penicillin; the other did not, necessitating installation of a pacemaker. Thus, permanent heart damage may result from cardiac involvement in Lyme disease.

Adult↗

The self-priming action of LHRH increases the low pituitary LH and FSH response caused by ovarian factors: observations in vitro.

Pituitary glands taken from intact rats on day 2 of dioestrus and incubated with LHRH show a biphasic pattern of LH and FSH release. Initially the release of the gonadotrophins is low (first-phase or lag-phase response), but increases during further incubation with LHRH (second-phase or primed-state response). Removal of the influence of an unidentified ovarian factor either by ovariectomy or prolonged incubation in medium only leads to an increased (lag-phase) response to LHRH. The development of the increased response after prolonged incubation was prevented by the addition of cycloheximide to the media, implicating that this process is dependent upon the synthesis of protein. Steroid-free material (bovine follicular fluid or rat ovarian extracts) prevented the development of this process. In addition, it was shown that steroid-free rat ovarian extracts were also able to induce the development of a lag phase in pituitary glands from ovariectomized rats. Finally, it was found that steroid-free ovarian extracts reversed the self-priming effect of LHRH. The biological activity which reduced the responsiveness of the pituitary gland towards stimulation by LHRH was eliminated after the use of protein-denaturating techniques such as increased temperature or addition of methanol. The presence of this activity in ovaries, did not vary during the oestrous cycle, contrary to inhibin-like activity. Hence the ovarian factor responsible for the low lag-phase response is a protein which is probably not identical to inhibin. It is concluded that a non-steroidal ovarian factor reduces the responsiveness of the anterior pituitary gland to LHRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Regulation by ovarian factors of the LHRH-induced LH response in pituitary glands in situ or grafted under the kidney capsule in intact and ovariectomized rats.

When pituitary glands from intact female rats are incubated with LHRH, the resulting LH release shows a biphasic pattern: an initial low rate of LH release (lag phase) is followed by a high rate. When pituitary glands from long-term ovariectomized rats are incubated, the rate of LH release is high throughout stimulation with LHRH. The disappearance of the lag phase might be due to increased LHRH release after ovariectomy and/or the disappearance of ovarian factors. To distinguish between these possibilities, pituitary glands which had been exposed to endogenous LHRH (pituitary glands in situ) or which had been unexposed to endogenous LHRH (pituitary glands transplanted under the kidney capsule) were incubated in the presence or absence of LHRH. Biphasic LH secretion patterns were observed during incubation with LHRH with the animal's own pituitary gland and with the transplanted pituitary gland from intact, but not from ovariectomized rats. Thus the disappearance of the lag phase after ovariectomy results from the absence of ovarian secretory products, rather than from increased release of LHRH.

Animals↗

Acute desensitization of pituitary FSH response to LHRH in ovariectomized rats: further evidence that in the presence of ovarian proteins the LHRH-dependent, LH-like component of FSH release becomes apparent.

Pulsatile release of LHRH and short-term pituitary desensitization to LHRH in the rat are believed to be necessary for the maintenance of LH pulsatility. In contrast, FSH release is partly induced by LHRH release and is partly LHRH-independent. This LHRH-independent release of FSH is subject to inhibitory feedback control by ovarian proteins (probably inhibin), and may obscure an LHRH-induced short-term loss of pituitary FSH responsiveness to LHRH. The object of this study was to establish whether short-term pituitary desensitization to single doses of LHRH results not only in a loss of LH response, but also of FSH response. Ovariectomized rats were used to eliminate the influence of steroid feedback. A group of ovariectomized rats was pretreated with steroid-free bovine follicular fluid (bFF) to suppress LHRH-independent FSH release, and phenobarbital to suppress LHRH-dependent FSH release respectively, 7 and 1 h before administration of LHRH. Another group received phenobarbital only. The animals were injected sequentially with either low or high doses of LHRH (1.25 or 10 ng/100 g body weight at times 0 and at 80, 120 or 180 min, and 6.25 or 50 ng/100 g at 60 min). Blood was taken for FSH measurements before and 5 and 10 min after each injection. Rats pretreated with bFF and phenobarbital showed an acute FSH response related to the dose of injected LHRH. No dose-response curve was seen in animals which had only been pretreated with phenobarbital.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effectiveness of rubidomycin in induction therapy with vincristine, prednisone, and L-asparaginase for standard risk childhood acute lymphocytic leukemia: results of a Dutch phase III study (ALL V). A report on behalf of the Dutch Childhood Leukemia Study Group (DCLSG).

The Dutch Childhood Leukemia Study Group (DCLSG) performed a phase III study-Study (ALL) V-to evaluate the effectiveness of rubidomycin in induction therapy with vincristine, prednisone, and L-asparaginase for children (0-15 years) with standard risk acute lymphoblastic leukemia (ALL) (white blood cell [WBC] counts less than 50.10(9)/L, absence of mediastinal mass, and/or cerebromeningeal leukemia). Furthermore, the influence of initial patient and disease characteristics on the outcome was analyzed. Between May 1979 and December 1982, 240 patients entered the study and were randomized into two groups: group A (n = 122) received induction treatment with vincristine (VCR), prednisone (Pred), and L-asparaginase (L-Asp); for group B (n = 118), induction therapy consisted of VCR, Pred, L-Asp, and rubidomycin (Rub). All patients subsequently underwent cranial irradiation (doses adjusted to age) in combination with intrathecal methotrexate; maintenance therapy of 6-mercaptopurine and methotrexate for 5 weeks followed by vincristine and prednisone for 2 weeks was given for 24 months. The complete remission (CR) rate was similar in both groups (94.5%). Event-free survival (EFS) 5 years after diagnosis was higher in group B (62.5 +/- 4.5%) than in group A (54.7 +/- 4.5%), although the difference is not significant (p = 0.20). A high initial WBC (greater than or equal to 10.10(9)/L), age (greater than or equal to 10 years), a low platelet count (less than 100.10(9)/L), and a positive acid phosphatase reaction of the leukemic cells were unfavorable prognostic factors (p less than 0.05). Sex, French-American-British (FAB) classification group, immunophenotype, and treatment in specialized centers did not have a significant impact on event-free survival.

Adolescent↗

Studies on a high molecular weight luteinizing hormone release stimulating factor of the ovine pineal gland.

Former work has shown that crude extracts of ovine pineal glands probably exert a stimulating activity on the release of gonadotropins of anterior pituitaries in vitro. By aqueous extraction followed by ultrafiltration through anisotropic membranes high Mr (above 100,000 daltons) fractions were obtained, which exhibit a stimulating effect on the levels of gonadotropins in the medium of either cultured pituitary cells or anterior hemipituitaries in short-term culture. Partial purification of a pineal luteinizing hormone release stimulating factor was accomplished by Sephadex G-150 filtration with a biopotency of 226 +/- 23 micrograms LH-RP-1 equivalents per mg protein and without an affinity for binding to anti-LHRH or anti-LH antibodies. The present data substantiate that high Mr forms, slightly heavier than authentic pituitary LH (Mr 23,000 daltons) and therefore not identical to the hypothalamic decapeptide LH-RH, represent ovine pineal factors which can increase the concentration of LH in the medium of cultured anterior pituitaries, but does not influence the secretion of prolactin in vitro.

Animals↗

The influence of pulsatile GnRH administration to the ovariectomized rat on the pituitary response to GnRH and the occurrence of spontaneous LH pulses.

Otherwise untreated adult ovariectomized rats were given pulses of GnRH (5 ng/100 g body weight iv) once every 60 or 120 min for 24 or 96 h. On the first and last day of the experiment plasma LH was estimated during the administration of GnRH pulses. Endogenous LH pulses between exogenously generated LH pulses were observed in nearly all animals on both the first and the last day, without any change in nadir and amplitude values. Shortly after an injection of GnRH, the spontaneous LH pulses were fewer than expected. The number of these pulses, however, increased again with time after the injections. The response to exogenous GnRH was reduced on the last day of the experiment. However, not all GnRH injections led to LH pulses. Most injections which did not result in an LH pulse appeared to be given within 15 min after a preceding endogenous LH pulse. The results obtained are in agreement with the hypothesis of an acute short-lasting desensitization of the pituitary gland caused by exogenous as well as endogenous pulses of GnRH.

Animals↗

Pulsatile GnRH treatment of the ovariectomized rat and release of LH and FSH.

The effect of pulsatile GnRH administration on the levels of LH and FSH was investigated in rats that had been ovariectomized 2 weeks earlier. Also the asynchronous occurrence of endogenous and GnRH-induced LH and FSH pulses was analysed. A small pulse dose of GnRH (1.25 ng/100 g) was given iv at a frequency of once every 60 min or once every 120 min during 24 h. A larger dose of 5 ng/100 g was given once every 60 or 120 min during either 24 h or 96 h. Blood was sampled arterially every 5 min around the two first and last GnRH injections and LH and FSH were measured. Only the treatment with the larger GnRH pulse dose resulted in a change of LH and FSH plasma levels. LH levels declined under all circumstances, whereas FSH was found to be increased temporarily after 24 h of treatment. The pituitary LH response to pulses of GnRH (5 ng/100 g) decreased irrespective of the frequency or duration with which GnRH was administered. There was a marked asynchronicity between LH and FSH pulses and almost every injection of GnRH (5 ng/100 g) resulted in clear LH pulses but not in FSH pulses.

Animals↗

[Results of treatment of children with acute lymphatic leukemia (ALL) according to the ALL V protocol of the Netherlands Working Group on Leukemia in Children].

The Dutch Childhood Leukemia Study Group performed a phase III study (Study ALL V) to evaluate the effectiveness of addition of rubidomycin to induction treatment with vincristine, prednisone and L-asparaginase in children (0-15 years) with standard risk acute lymphoblastic leukemia: WBC less than 50.10(9)/l, absence of mediastinal mass and/or cerebromeningeal leukemia. Furthermore, the influence of some initial patient- en disease-characteristics on the outcome was analysed. Between May 1979 and December 1982 240 patients entered into the study and were randomized into 2 groups: group A (n = 122) received induction treatment with vincristine, prednisone and L-asparaginase; group B (n = 118) received induction treatment with vincristine, prednisone, L-asparaginase and rubidomycin. All patients received cranial irradiation (doses adjusted to age) and intrathecal methotrexate, followed by maintenance treatment with 6-mercaptopurine and methotrexate for 5 weeks, alternated with vincristine and prednisone for 2 weeks, up to 24 months. Complete remission rate was 94% in both groups. Event-free survival at 5 years after diagnosis was higher in group B (62% +/- 4.6%) than in group A (54.2% +/- 4.6%) but the difference was not significant. A higher initial WBC, age greater than or equal to 10 years and a positive acid phosphatase reaction of the leukemic cells were unfavorable prognostic factors (p less than 0.01). Sex, FAB-morphology, immunophenotype and place of treatment (center or general hospital) were not significant factors.

Antineoplastic Combined Chemotherapy Protocols↗

Short-term pituitary desensitization to luteinizing hormone-releasing hormone (LH-RH) after pulsatile LH-RH administration in women with amenorrhea of suprapituitary origin.

The existence of a short-term pituitary desensitization in luteinizing hormone (LH) release to single doses of luteinizing hormone-releasing hormone (LH-RH) in the ovariectomized rat was recently disclosed. The purpose of the present study was to investigate whether this refractoriness is also present in humans. Blood from six women with amenorrhea of suprapituitary origin was sampled every 10 minutes for 300 minutes for determination of LH and follicle-stimulating hormone (FSH). A pulse of 20 micrograms LH-RH was given intravenously 90 and 210 minutes after the first blood sample, and 2 micrograms LH-RH was given 30, 150, 240, and 270 minutes after t0. The mean maximal increments of LH and FSH were compared. The LH response to a 2-micrograms LH-RH bolus given 30 (t240) or 60 (t150) minutes after a 20-micrograms LH-RH pulse was significantly decreased, compared with the initial response to this dose at t30. For both LH and FSH, the response to 2 micrograms LH-RH given 30 minutes after the 20-micrograms pulse (t240) was almost absent, compared with 60 (t150) minutes after the 20-micrograms dose. We conclude that a short-term pituitary refractoriness to LH-RH is present after administration of single pulses of LH-RH in women with amenorrhea of suprapituitary origin and pulses of LH-RH in the physiologic range (2 micrograms) given to these women do not always generate LH and FSH increments that are identifiable as significant hormone pulses.

Adult↗

In vivo release of dopamine, luteinizing hormone-releasing hormone and thyrotropin-releasing hormone in male rats bearing a prolactin-secreting tumor.

The present study was concerned with the effects of a transplantable prolactin-secreting pituitary tumor (7315b) on the hypothalamic release of dopamine, luteinizing hormone-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) in gonadectomized, adrenalectomized male rats bearing subcutaneously a testosterone capsule and a corticosterone pellet. Similar male rats not inoculated with tumor served as controls. The rats were studied 3-4 weeks after tumor inoculation, while they were anesthetized with urethane. Compared to the controls, prolactin levels in the tumor-bearing rats had increased 70-fold, whereas the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) decreased to 20 and 27%, respectively. In tumor-bearing rats, the secretion of dopamine into hypophysial stalk plasma increased from 2.3 to 4.9 ng/h (p less than 0.025), whereas that of LHRH decreased from 127 to 52 ph/h (p less than 0.005). Since the use of urethane anesthesia may change quantitatively and qualitatively the effects of hyperprolactinemia, it was decided to study these effects on the in vivo release of LHRH, dopamine and TRH in conscious rats by a push-pull perfusion of the median eminence-arcuate nucleus area. Using this technique, it was found that in tumor-bearing rats the secretion of LHRH decreased from 20.0 to 9.8 pg/15 min (p less than 0.005), whereas that of dopamine increased from 118 to 246 pg/15 min (p less than 0.025). The secretion of TRH was not altered by hyperprolactinemia (4.1 vs. 4.4 pg/15 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

Phenobarbital enhances pituitary LH release induced by LRH pulses in the ovariectomized rat.

In the ovariectomized (OVX) rat, the plasma LH response was measured to a pulse of LRH (1.25 or 5 ng/100 g body weight, ia) given before and 1 h after ip administration of phenobarbital (80 mg/kg body weight). The LH response to the LRH pulses was increased 1 h after phenobarbital. In a second experiment, the pituitary LH content of OVX rats was measured 1 h after administration of phenobarbital or saline. No difference in pituitary LH content was found. It is concluded that in the OVX rat, phenobarbital increases the response to a pulse of LRH, presumably by suppressing endogenous pulsatile LRH. This, together with results of earlier experiments, further supports the hypothesis that under conditions where endogenous pulsatile LRH is present, there is always a certain degree of pituitary desensitization or refractoriness and that the removal of this endogenous LRH leads to recovery of pituitary sensitivity to LRH.

Animals↗

Suppression by LRH of the stimulatory effect of oestradiol on the secretion of LH by the rat pituitary gland.

Ovariectomized rats were infused with varying doses of luteinizing hormone-releasing-hormone (LRH). Some of the rats were also treated with oestradiol benzoate (EB). The effects of these pre-treatments on the in vitro release of luteinizing hormone (LH) were studied. The following parameters of in vitro LH release were measured: the autonomous secretion rate; the secretion rate following maximum stimulation with LRH, and the total quantity of LH released during the 6-hour experiment. The in vivo pre-treatments with LRH and EB dose-dependently decreased the pituitary LH content as well as all three of the above parameters of in vitro LH secretion. There was a linear relationship between the pituitary LH content and the three parameters of in vitro LH release. These parameters were therefore expressed as percentage of the pituitary LH content to give the relative LH secretion rates. The three parameters were thereby corrected for LRH/EB-induced changes in the pituitary LH content. In this way we obtained information on the effects of LRH and EB on the state of the LH release mechanisms of the gonadotropes. EB potentiated the LRH-induced depletion of the pituitary LH stores at all in vivo LRH infusion rates. The effect of EB on the quantity of LH released during perifusion in vitro, however, varied with the previous LRH infusion rates. After LRH infusion rates lower than about 120 ng/h (which establishes plasma concentrations of about 70 ng/l) EB enhanced the stimulated quantity of LH released. After higher rates of LRH infusion, EB lowered the amount of LH released.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗