PubMed Health⌕ Search

Biomedical subjects

J Knittle

Publications and source records attributed to J Knittle.

9 recordsLinked to original sources
PubMed1998

LHRH antagonists.

After almost two decades, the research on LHRH antagonists has produced a number of decapeptides that are currently in clinical studies. The structures of these antagonists, unlike the agonists, differ substantially from that of LHRH. Five of the ten amino acids are unnatural and of D configuration. The structural combination of a hydrophobic N-terminus (residues 1, 2, and 3) and a basic/hydrophilic C-terminus (residues 6 and 8) was thought to be responsible for some HR reactions encountered with the second generation of LHRH antagonists. This side effect was greatly reduced by substituting the appropriate combination of amino acids at positions 5, 6, and 8. The next hurdle in the drug development of LHRH antagonists was solubility and aggregation. In the case of A-75998, water solubility was improved by 12- to 25-fold via substitution of NMeTyr at position 5. However, based on DLS analysis, the aqueous solutions still contained some large aggregates that were not visible to the naked eye. This formation of aggregates was eliminated on formulating A-75998 in Encapsin. In men, a single s.c. dose of 2 mg of A-75998 suppressed T to the castrate levels for over 30 hr. Other LHRH antagonists including ganirelix and cetrorelix are also in phase I/II clinical studies. Clinical studies with cetrorelix in prostate cancer; in vitro fertilization, and benign prostate hypotrophy have been reported.

Animals↗
PubMed1994

In vitro and in vivo activities of reduced-size antagonists of luteinizing hormone-releasing hormone.

A novel series of octapeptide LHRH antagonists was designed on the basis of the structure of the (2-9) fragment of a LHRH agonist. By adopting a systematic SAR study, we were able to improve first the in vitro activity and then the in vivo LH suppression, raising them up to the range of the decapeptide antagonists NalGlu (51) and A-75998 (50), resulting in A-76154 (49). The octapeptide antagonist A-76154 is the most potent reduced-size LHRH antagonist reported. It suppresses LH in the castrated rat by over 80% for a period of 4 h following sc bolus administration of 30 micrograms/kg.

Amino Acid Sequence↗
PubMed1990

Lupron depot (leuprolide acetate for depot suspension) in the treatment of endometriosis: a randomized, placebo-controlled, double-blind study. Lupron Study Group.

The safety and efficacy of leuprolide acetate (LA) for depot suspension (Lupron depot; TAP Pharmaceuticals, North Chicago, IL), 3.75 mg versus placebo, in the treatment of pain associated with endometriosis was assessed in a randomized, double-blind, multicenter study involving 52 patients. Dysmenorrhea, pelvic pain, and pelvic tenderness all responded significantly to LA treatment in comparison with placebo. Menses were suppressed in all of the LA patients. Estradiol decreased significantly to menopausal levels in the LA group. There were small to moderate changes in a variety of laboratory parameters, but these were not clinically significant. The most common adverse event was vasodilatation, occurring significantly more frequently in the LA group. Lupron depot was shown to be safe and effective in inducing a hormonal and menstrual suppression in patients with endometriosis, resulting in alleviation of pain symptoms.

Adult↗
PubMed1984

Do fat cell morphometrics predict weight loss maintenance?

A comprehensive psychosocial approach was used to treat 44 otherwise healthy obese patients, 49-332 percent above desirable weight, whose fat cell morphometrics arbitrarily placed them into three groups: seven with predominant fat-cell hypertrophy, 18 with predominant hyperplasia, and 19 with mixed hypertrophy and hyperplasia. Continuous psychological support was provided to all patients, and life-style was altered by nutrition education and behavior modification. Psychiatric referral was made when indicated. Four of the 45 patients, who were refractory to treatment, were referred for surgery. Successful treatment was defined as maintenance of a weight loss of 18 kg or more for one year. Two of the seven hypertrophic, seven of the 18 hyperplastic, and 11 of the 19 mixed hypertrophic-hyperplastic patients had successful results without surgery. Overall success rate was 45 percent, and did not differ significantly according to fat cell morphometrics. Although greater weight losses were maintained in correlation with the extent of hyperplasia P less than 0.005, the percentage weight change from intake weights was similar. In summary, a program of continuous psychological support, nutrition education, and behavior modification resulted in a substantially higher rate of successful one-year maintenance of weight loss than is generally reported for the treatment of markedly obese patients. Further long-term follow-up is in progress. In contradiction to predictions based on adipose cell morphometrics, those patients with simple hypertrophy of their fat cells were not more successful in maintaining a weight change. Although maintenance varied from 18.2 kg to 52 kg for those successfully treated, a weight loss of approximately 20 percent of the intake was sustained.

Adipose Tissue↗
PubMed1978

A simple technique for fat biopsy of PBB-exposed individuals.

A simple nonsurgical technique of obtaining fat samples by aspiration from the gluteal prominence was developed by Hirsh in 1960 and has been in use in our Nutrition Clinic at the Mount Sinai Hospital for several years. We have modified it for field use and the analysis of fat-soluble hydrocarbon residues. All the materials which will contain the fat sample to be analyzed are washed with acetone and pesticide residue-free hexane, and a 15 gauge needle and 33 cc syringe are sterilized. Aspiration of fat from the lateral gluteal prominence is accomplished under local xylocaine anesthetic. The anesthetic also serves as the vehicle into which the fat is broken by the shearing action of the 15 gauge needle. Fat particles are sucked into the syringe by a constant vacuum kept on the syringe during lateral movement of the needle under (and parallel to) the skin within the gluteal fat pad; 200--500 ml of fat can be obtained for hydrocarbon residue analysis. The only complications have been some mild hematomas at the site of the aspiration. The method avoids surgical biopsy and sutures and takes about 7--8 min.

Adipose Tissue↗