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Biomedical subjects

C Gottlieb

Publications and source records attributed to C Gottlieb.

At least 37 records · Page 2Linked to original sources
PubMed1997

Delayed puberty in girls with cystic fibrosis despite good clinical status.

BACKGROUND: Previous studies have shown that puberty is delayed among patients with cystic fibrosis (CF). Malnutrition has been considered the main etiologic factor. Today with improved medical therapy and nutritional support, most CF patients obtain an almost normal nutritional status. OBJECTIVES: To investigate whether pubertal development among female CF patients at the Stockholm CF Center was normal and, if not, what other parameters besides nutrition might influence this. METHODS: Seventeen patients were studied retrospectively regarding age at peak height velocity and menarche. Menarcheal age (MA) was compared with normal population data and related to clinical and nutritional status, genotype, oral glucose tolerance test (OGTT), and essential fatty acid levels. RESULTS: The mean age at peak height velocity (12.9 +/- 0.8 years) and at menarche (14.9 +/- 1.4 years) was significantly higher in the CF patients compared with normal controls (11.9 +/- 1.0 years and 13.0 +/- 1.0 years, respectively). No correlation was found between menarchal age and nutritional or clinical parameters. The patients with pathological OGTT without overt diabetes were significantly older at menarche (15.8 +/- 1.7 years) compared with the patients with normal OGTT (14.3 +/- 0.9 years). The patients who were homozygous for the most common mutation, deltaF508, were significantly older at menarche (15.2 +/- 1.9 years) than those who were not (14.7 +/- 0.9 years). CONCLUSIONS: Pubertal delay still existed among the CF patients despite good clinical status. The patients homozygous for deltaF508 and those with pathological OGTT showed the most delayed puberty.

Adolescent↗
PubMed1996

Progesterone stimulates GABA uptake in human spermatozoa.

Progesterone can initiate the mammalian sperm acrosome reaction in vitro, and studies on the effect of progesterone and several other steroids have demonstrated an increased calcium influx following binding to the sperm membrane. We have previously presented data indicating the presence of a GABA transport protein in human spermatozoa. In this study, we have examined the uptake of radiolabelled GABA into human spermatozoa in the presence of progesterone, other steroids known to elevate intracellular calcium, and steroids known to be ineffective as stimulators of calcium influx. The results demonstrate a twofold increase in GABA uptake following preincubation with progesterone or steroids known to stimulate calcium influx. Steroids with minor effects on calcium influx were less effective as stimulators of GABA uptake.

Biological Transport↗
PubMed1996

The results of atrial flutter ablation in patients with and without a history of atrial fibrillation.

To determine the impact of atrial flutter radiofrequency catheter ablation on recurrence of atrial flutter and atrial fibrillation, 32 patients with atrial flutter (18 with a history of atrial fibrillation) were followed for a mean of 8.6 months; atrial flutter has not recurred after 1 (26 patients) or 2 (5 patients) successful ablation procedures. Atrial flutter did not appear proarrhythmic for atrial fibrillation, with only 1 of 15 patients without a history of atrial fibrillation developing the arrythmia in the absence of an alcohol binge or cocaine use.

Atrial Fibrillation↗
PubMed1996

Carrier-mediated gamma-aminobutyric acid uptake in human spermatozoa indicating the presence of a high-affinity gamma-aminobutyric acid transport protein.

Human spermatozoa are capable of a carrier-mediated gamma-aminobutyric acid (GABA) uptake. The uptake is dependent on the concentration of Cl- and Na+ in the external medium, and the kinetics of the carrier resembles high-affinity GABA transport proteins. The time-dependent uptake of GABA displays large interindividual differences and is not correlated to motility parameters or morphology in the individual sample. Incubation of human spermatozoa with radiolabeled GABA was performed. Swim-up preparations of human spermatozoa were incubated with [3H]GABA, and subsequent GABA uptake was measured at various times by scintillation counting. GABA was accumulated intracellularly, and the uptake could be inhibited by preincubation of the samples in 200 microM nipecotic acid. Addition of aminooxyacetic acid in the medium did not alter the results, indicating that the internalized GABA remained unmetabolized intracellularly throughout the observation period. Kinetic analysis of GABA uptake was performed, and the Km for GABA transport was 14 microM. GABA uptake was reduced by equimolar substitution of NaCl in the capacitating medium by KCl, choline chloride, LiCl, N-methyl-D-glucamine (HCl) or D-glucuronic acid (sodium salt). Maximal reduction of [3H]GABA uptake was observed when the Na+ fraction of the medium was replaced with KCl. The results indicate the presence of a high-affinity GABA transport protein in the plasma membrane of human spermatozoa. GABA uptake was subsequently measured in 30 individual semen samples from men of barren couples. Large interindividual differences in GABA uptake was observed, but GABA uptake was not correlated to motility parameters or to morphology in the individual samples analyzed.

Carrier Proteins↗
PubMed1996

Hormonal regulation of serum lipoprotein (a) levels: effects of parenteral administration of estrogen or testosterone in males.

When given orally, estrogens, as well as androgens, lower serum lipoprotein (a)[Lp(a)]levels. To determine whether these effects occur also after parenteral administration of steroids, Lp(a) levels were determined in two groups of elderly males suffering from prostatic carcinoma, who were randomized to treatment with parenteral estrogen (n = 8) or orchidectomy (n = 6). One group of healthy male volunteers (n = 9) was studied after parenteral administration of testosterone. Estrogen was given as im polyestradiol phosphate, 240 mg twice monthly, and testosterone was given as im injections, 250 mg/week. In the orchidectomized subjects, Lp(a) levels increased by 20% by month 3 after treatment (P < 0.05). In spite of drastic changes in serum hormone levels, no change in Lp(a) levels was observed in the estrogen-treated subjects. Concomitantly, low-density lipoprotein cholesterol levels were lowered by 15% and high-density lipoprotein cholesterol levels increased by 20%. Testosterone administration lowered Lp(a) levels by 20% (P < 0.05). No significant changes in serum lipid levels were observed in the testosterone-treated subjects or in the orchidectomy group. Thus, during parenteral administration of estrogens or androgens, diverging effects on Lp(a) and serum lipoproteins were observed. In particular, the mode of administration of estrogen influenced the response in Lp(a) levels. This suggests that the regulatory role of sex hormones on serum Lp(a) levels may depend on their capability to influence hepatic metabolic pathways of Lp(a).

Adult↗
PubMed1995

Serum and urinary markers of exogenous testosterone administration.

In an attempt to find optimal markers of exogenous testosterone (T) administration in male athletes, a number of compounds were measured in 11 healthy men before and after 3, 6 and 9 months of weekly administration of 250 mg i.m. T enanthate and in age-matched untreated controls. The following variables were measured in serum: T, 17 alpha-hydroxyprogesterone (17-OHP), sex hormone-binding globulin (SHBG), estradiol-17 beta, estrone (free + conjugated) and luteinizing hormone (LH). The following variables were measured in urine: T glucuronide (urinary T), epitestosterone glucuronide (urinary epiT), estrone (free + conjugated) and LH. Serum T, serum T/17-OHP ratio, serum T/LH ratio, serum T/SHBG ratio, serum and urinary estrogens, urinary T/creatinine-, T/epiT- and T/LH ratios increased whereas serum 17-OHP, SHBG and LH and urinary epiT/creatinine- and LH/creatinine-ratios decreased significantly during treatment. Levels above the upper reference limit were found in all subjects at 3, 6 and 9 months for serum T/17-OHP and serum and urinary T/LH ratios and at 6 months for the urinary T/epiT ratio. Levels below the lower reference limit were found in all subjects at 3, 6 and 9 months for serum LH and the urinary LH/creatinine ratio, at 3 months for the urinary epiT/creatinine ratio and at 9 months for serum 17-OHP. No other variable showed abnormal values in all subjects at the same occasion. Despite significant changes during treatment, steroid concentrations as such are poor indicators of T doping. Serum and urinary LH levels, T/LH ratios and serum T/17-OHP ratios seem to be the most reliable markers of exogenous T administration in males.

Age Factors↗
PubMed1995

Evidence for gamma-aminobutyric acid specific binding sites on human spermatozoa.

The possible presence of gamma-aminobutyric acid (GABA) specific binding sites on human spermatozoa was investigated. Swim-up preparations of human spermatozoa were incubated with radiolabelled GABA in the presence of unlabelled GABA, alternatively displacers of GABAA/B receptors and GABA transport proteins. The results indicate that GABA specific binding sites are present on the surface of human spermatozoa, and that these binding sites possibly indicate the presence of GABA transport proteins. Furthermore, GABA at different concentrations was added to swim-up preparations of human spermatozoa. Possible effects of GABA on sperm motility, hyperactivation and acrosome reaction were explored. No significant differences were observed between treated groups and controls concerning motility parameters and hyperactivation. Incubation with GABA did not cause any increase in spontaneous acrosome reaction. However, spermatozoa treated with the calcium ionophore A-23187 showed a small but significantly increased ability to undergo the acrosome reaction following preincubation in 10(-4) M GABA (P < 0.05).

Acrosome↗
PubMed1994

The use of progesterone antagonists in combination with prostaglandin for termination of pregnancy.

Antiprogestin alone is not sufficiently effective in terminating early pregnancy to be clinically useful. The only exception seems to be immediate post-ovulatory administration which inhibits endometrial development to an extent that prevents implantation of the fertilized ovum. During early pregnancy the uterus is inactive. Treatment with antiprogestin with result in an increased uterine contractility and a significant increase of myometrial sensitivity to prostaglandin. The effect is probably mainly due to the release of the inhibitory effect of progesterone. Antiprogestin not only activates the uterus, it also causes a ripening of the cervix. The combination of RU486 and either vaginal administration of gemeprost or i.m. injections of nalador provide a safe and effective medical abortion in the first 8 weeks of pregnancy. Recent clinical studies indicate that it may be possible to replace the prostaglandin analogues in current use by the orally active analogue misoprostol. Misoprostol is inexpensive and stable at room temperature and would facilitate the provision of medical abortion with mifepristone. Experimental data also indicate that a combination of RU486 and misoprostol may be developed into an effective once-a-month late luteal method to regulate fertility. Pre-treatment with RU486 is also useful in later stages of gestation. A combination of RU486 and the vaginal administration of gemeprost is a highly effective, safe and simple non-invasive method for terminating both early and late second trimester pregnancy.

Abortifacient Agents, Steroidal↗
PubMed1993

Radiosensitization of uterine cancer cell lines by cytotoxic agents.

Radiotherapy remains an integral part of uterine cancer therapy. Overcoming radioresistant tumors by sensitizers continues to be a prime objective in radiotherapy research. In this study, the effects of five cytotoxic agents on two radiosensitive and four radioresistant uterine cancer cell lines were investigated. The ATP bioluminescence was used to measure surviving fractions. Data analysis was done using the linear quadratic model and radiosensitivity index D. Both AN3 and SKUT1B were radiosensitive with Ds of 1.73 and 1.72 Gy, respectively. The resistant cell lines had the following D values: AE7, 3.50; ECC, 6.61; HEC1A, 4.59; and HEC1B, 13.49 Gy. The average radiosensitization effects for various drugs were measured by reduction of D: DXR 45 +/- 7, DDP 40 +/- 9, 5FU 55 +/- 10, MITO 59 +/- 14, and HU 1.7 +/- 7%. Except for HU, Wilcoxon analyses revealed that these sensitizing effects were significant with P < 0.02. In summary, Adriamycin, 5-fluorouracil, cisplatin, and mitomycin-C have the potential to be radiosensitizers in uterine cancer cell lines.

Adenosine Triphosphate↗
PubMed1993

Cardioverter-defibrillator systems implanted without thoracotomy: radiographic findings.

Ventricular arrhythmias are the primary cause of sudden death from heart disease in the United States. In the past decade, management of these arrhythmias has been revolutionized by the development of implantable cardioverter-defibrillators (ICDs). Earlier devices required thoracotomy for implantation (Fig. 1). Complications associated with the earlier devices include pneumothorax, pleural effusion, mediastinal infection, and, notably, crinkling of the patch and migration. The morbidity of median sternotomy has led to the development of ICDs that can be implanted without thoracotomy. We illustrate the normal radiographic appearance and complications of two recently developed ICD lead systems.

Adolescent↗
PubMed1992

5-chlorodeoxycytidine, a radiosensitizer effective against RIF-1 and Lewis lung carcinoma, is also effective against a DMBA-induced mammary adenocarcinoma and the EMT-6 tumor in BALB/c mice.

5-Chlorodeoxycytidine (CldC), coadministered with modulators of pyrimidine metabolism, is an effective radiosensitizer of murine tumors. Past studies that utilized RIF-1 tumors in C3H mice and Lewis lung carcinoma (LLC) in BDF1 mice have been extended with an emphasis on using multiple cycles of drug administration followed by irradiation of LLC and the use of two additional tumor models. Four of seven cures of BDF1 mice bearing LLC were obtained with three doses of 20 Gy irradiation, in which the first and third dose were preceded by a "Standard Protocol" that includes N-(phosphonacetyl)-L-aspartic acid (PALA), 5-fluorodeoxycytidine (FdC), tetrahydrouridine, and the radiosensitizer, 5-chlorodeoxycytidine. No cures were obtained in groups of mice receiving radiation alone or drugs alone, and there were no "no takes" in untreated control groups (six mice/group). Extensive tumor inhibition, exceeding that obtained with drugs or radiation alone, was obtained with two cycles of drugs and radiation combined when a dimethybenzanthracene-induced mammary adenocarcinoma was used in BALB/c mice. With the EMT-6 tumor in BALB/c mice, doses of 10 and 20 Gy were administered 9 and 16 days after tumor implantation, each preceded with the Standard Protocol; this resulted in a tumor growth delay of 24 days. No tumor growth delay occurred with drugs or radiation alone. The omission of PALA, FdC or CldC from the Standard Protocol resulted in loss of tumor control, which was obtained with the complete protocol. The fact that 5-chlorodeoxycytidine is an effective radiosensitizer in four rodent tumor systems is compelling evidence that it has potential as a radiosensitizer of human tumors, especially in view of its tumor selectivity and its resistance to catabolism when used with modulators of its metabolism, and in view of the high levels of the key enzymes in human tumors, which can convert 5-chlorodeoxycytidine to 5-chlorodeoxyuridine triphosphate, the proximate radiosensitizer.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Cytomorphometric analysis of small cell neoplasms of the lung from specimens obtained via bronchoscopy.

Primary neoplasms of the lung composed of small cells consist of undifferentiated small cell carcinoma (UCS), carcinoid tumors (CT) and some non-small cell carcinomas (NonSC) that lack cytoplasmic differentiation. The cytologic identification of tumors from specimens obtained via bronchoscopy sometimes presents difficulties due to overlapping patterns. In order to define additional differentiating criteria, we evaluated Papanicolaou-stained smears from 30 histologically proven cases, 10 from each of the three groups, with statistical analysis of computer-assisted morphologic measures. We identified significant differences between NonSC versus USC and NonSC versus CT with regard to nuclear and cytoplasmic dimensions (P less than .0001) but not between USC and CT. The nuclear:cytoplasmic ratios were similar in all three groups (P = .39). From this preliminary study we conclude that morphometric analysis can distinguish NonSC from USC and CT but not USC from CT.

Biopsy↗
PubMed1991

The effect of 19-hydroxy prostaglandins on the human myometrium in vitro.

Human semen contains high amounts of different prostaglandins of which the quantitatively dominating compounds are 19-hydroxy PGE and 19-hydroxy PGF. The effect of PGE and PGF on the contractility of the human uterus is well known whereas the corresponding 19-hydroxy derivatives have not previously been examined in detail. In the present investigation 19-hydroxy PGE1 was shown to dose-dependently decrease the frequency and the amplitude of the contractions in human myometrial tissue in vitro. The effect of seminal 19-hydroxy prostaglandins may thus be of importance for sperm transport through the female genital tract.

Alprostadil↗
PubMed1991

The fertility potential of male cystic fibrosis patients.

Men suffering from cystic fibrosis (CF) are considered to be infertile because of azoospermia. In testicular biopsies from two patients with CF normal spermatogenesis was found despite the absence of sperm in the ejaculate. Fructose and prostaglandin were not detectable in the semen whereas the levels of acid phosphatase and zinc were within normal limits, indicating normal prostatic function and absence of seminal vesicles. These findings may improve the possibility for male patients with CF to father a child.

Adult↗
PubMed1991

Uterine contractility and interaction between prostaglandins and antiprogestins. Clinical implications.

It is generally believed that progesterone and PGF2 alpha are of major importance in the regulation of uterine contractility. The results summarized herein indicate that progesterone withdrawal is essential for the changes in uterine contractility normally observed during the secretory phase of the menstrual cycle and that the inactivity of the early pregnant uterus is progesterone dependent. Treatment with the antiprogestin RU486 will convert the inactive early pregnant uterus to an active organ and will increase the sensitivity of the myometrium to prostaglandin. These latter effects of antiprogestin have resulted in the development of highly effective, nonsurgical procedures to terminate early pregnancy based on a combined treatment with RU486 and different PG analogues administered orally, vaginally, or intramuscularly. RU486 also has a softening effect on the cervix as demonstrated in late first trimester of pregnancy. This effect may be useful as pretreatment to vacuum aspiration in late first and early second trimester abortion performed by vacuum aspiration or dilatation and curettage. In prostaglandin-induced second trimester abortions, pretreatment with RU486 will significantly reduce the induction-to-abortion interval and the dose of prostaglandin needed.

Abortion, Induced↗
PubMed1991

Mucociliary function following sinus mucosal regeneration.

To evaluate sinus mucosal regeneration and cilia motility after surgical removal, 15 rabbits underwent unilateral removal of maxillary sinus mucosa. The opposite sinus served as an unoperated control. After 10 weeks, specimens were taken for examination from all operated on and control sinuses. Light, dark-field, and electron microscopy were performed. Mucosa from eight of the 15 sinuses operated on showed ciliary regeneration by light microscopy; six of these exhibited motile cilia on dark-field examination. Histopathologic findings of marked fibrosis, decreased seromucinous glands, and significant inflammation were commonly present in the sinuses operated on. Electron microscopy revealed frequent abnormalities, including complex and edematous cilia and fewer than normal cilia per unit area compared to controls. The dark-field, light, and electron microscopic findings of the regenerated, post-surgical mucosa are discussed.

Animals↗
PubMed1991

Vacuum aspiration for termination of early second trimester pregnancy after treatment with vaginal prostaglandin.

Vaginal and intramuscular administration of prostaglandin analogues are routinely used for dilatation of the cervical canal prior to vacuum aspiration in first trimester abortion. Whether the same procedure is also useful during the first weeks of the second trimester has been much less investigated. In the present study, 127 women in the 13th and 14th week of pregnancy were pretreated with 3 mg 9-deoxo-16,16-dimethyl-9-methylene PGE2 administered vaginally 12 hours before surgery. At surgery the cervical canal was dilated to 9.8 mm +/- 2.5 mm (mean +/- SD) and the evacuation of the uterus was uneventful. In 21% of the patients vaginal bleeding occurred prior to the operation. The mean blood loss at surgery was 49 ml and exceeded 100 ml in only 6 patients. Gastrointestinal side effects were rare but analgesic injections were demanded by 29% of the patients during the pretreatment period. No subsequent curettage was performed during the follow-up period but 2 patients (1.6%) were readmitted because of post-abortion endometritis. It can be concluded that after pretreatment with PG, vacuum aspiration can be safely performed during the first weeks of the second trimester.

16,16-Dimethylprostaglandin E2↗