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Biomedical subjects

P Klein

Publications and source records attributed to P Klein.

At least 19 recordsLinked to original sources
PubMed1992

O3-(2-carbomethoxyallyl) ethers of opioid ligands derived from oxymorphone, naltrexone, etorphine, diprenorphine, norbinaltorphimine, and naltrindole. Unexpected O3-dealkylation in the opioid radioligand displacement assay.

O3-(2-Carbomethoxyallyl) ether derivatives of some phenolic 4,5-epoxymorphinan opioid ligands have been prepared in a simple one-step procedure, and their behavior in the radioligand receptor assay was compared to their phenolic precursors. These O3-ether ligands appeared to show significant affinity for opioid receptors, about 2-fold less than the parent phenols, and their receptor selectivities were similar. However, on close examination of the stability of a representative ether 2b in the radioligand displacement assay, considerable O3-dealkylation was observed. The dealkylation process occurred even after denaturation of the proteins of the membrane preparation, and it occurred in the presence of model nucleophiles imidazole and thiophenol. Thus, what apparently was unusual activity is explained by O3-dealkylation to the parent phenol (e.g., 2a). Saturated ether analog 2c was not dealkylated under the conditions of the radioligand displacement assay and was a very weak opioid ligand. We conclude that the conversion of the O3(2-carbomethoxyallyl) ether electrophilic ligands to their parent phenols accounts for their activity in the opioid radioligand displacement assay.

Alkylation↗
PubMed1992

Delta opioid antagonist activity and binding studies of regioisomeric isothiocyanate derivatives of naltrindole: evidence for delta receptor subtypes.

The isothiocyanate group was attached to the 4'-, 5'-, 6'-, or 7'-position of naltrindole in an effort to determine the importance of the position of this electrophilic group on the selectivity for subtypes of delta opioid receptors. All of the ligands were delta-selective when tested against standard agonists in smooth muscle preparations. However, the rank-order delta antagonism of antinociception in mice did not parallel the in vitro pharmacologic data. The 5'-isothiocyanate 2 was the most potent and selective antagonist in vivo, causing a 52-fold increase of the ED50 for [D-Ser2,D-Leu5]enkephalin-Thr6 (DSLET) and no increase for [D-Pen2,D-Pen5]enkephalin (DPDPE). The effect of each of the ligands on the binding of [3H]DSLET and [3H]DPDPE to guinea pig brain membranes clearly differentiated between the binding sites that recognize these radioligands. These studies provide additional evidence for the presence of two subtypes of delta opioid receptors.

Animals↗
PubMed1992

Electrophilic opioid ligands. Oxygen tethered alpha-methylene-gamma-lactone, acrylate, isothiocyanate, and epoxide derivatives of 6 beta-naltrexol.

O6-Ether derivatives of 6 beta-naltrexol in which the ether substituent includes various electrophilic groups have been synthesized in an effort to examine structure-activity requirements at the 6 beta-substituent for receptor affinity and irreversibility of binding in opioid receptor preparations. A series of tethered 6 beta-ethers having terminal epoxides, alpha-methylene-gamma-lactones, and an isothiocyanate group were prepared. The stereochemistry of the alpha-methylene-gamma-lactones was established by convergent synthesis of their reduction products from epoxides of known absolute stereochemistry. In general, the tested compounds showed comparable affinity and selectivity for the receptor subtypes. All were found with high affinity for mu-sites. The terminal epoxide ether diastereomers 8 and 9 were not bound irreversibly in the assay for total opioid receptors. The alpha-methylene-gamma-lactone diastereomers 10 and 11, and their O14-acetyl precursors 20 and 21, respectively, varied in their irreversible effects, but where noted these effects were mu-site selective. Methacrylate ether 7 and isothiocyanate ether 12 were bound irreversibly at both mu- and delta-sites.

Acrylates↗
PubMed1992

Outcome and cost analysis of scheduled versus emergency scleral buckling surgery.

BACKGROUND: Retinal detachments are usually considered to be a surgical emergency. However, there are additional risks and costs for unnecessary emergency surgeries. The purpose of this study is to evaluate whether the conventional wisdom for treating all retinal detachments as emergencies needs to be re-examined. METHODS: Forty-eight patients who had an emergency scleral buckle and 89 patients who had a scheduled procedure were randomly selected from 884 consecutive patients who had a primary scleral buckling procedure during a 4 1/2-year period. The medical records of each patient were used to obtain detailed information related to prognosis. The visual acuity measurements of each patient, taken 6 months after the procedure, were obtained from the records of the ophthalmologist following the patient. Linear regression analysis was used to compare the final visual outcome for patients who had emergency surgery with patients who had scheduled surgery after taking into account patient factors related to prognosis. RESULTS: Patients selected for emergency surgery had better visual prognoses than scheduled patients but had the same risk of systemic complications and the same extent of detachment if the macula was not involved. None of the 18 patients with an attached macula experienced macular involvement while awaiting scheduled surgery. There were no differences between emergency and scheduled patients in ocular or systemic complications, rate of reattachment, rate of decreased visual acuity after surgery, visual outcome adjusted for prognosis, or, since 1985, length of hospital stay. A greater cost was incurred for the patients having emergency surgery due to difference in pay scales for support personnel. CONCLUSIONS: Because the study is not large and the patients were not randomized to treatment, the results are not definitive. However, they suggest that emergency surgery is unnecessary for many patients with a detached retina.

Appointments and Schedules↗
PubMed1992

[Techniques and experiences in funnel chest operations].

Hegemann's technique of funnel chest correction using transsternal metal bar stabilization was adapted from the method published by Sulamaa and coworkers in 1958. Until the end of 1991, about 2400 chest wall corrections were performed in our department, more than 2000 of them using modifications of the original method. The principles of external chest wall measurement, our classification method, and the current operative modifications are described. In long-term follow-up examinations less than 3% recurrences should be possible.

Adolescent↗
PubMed1992

[24-hour blood pressure changes in elderly people with isolated systolic hypertension, essential hypertension and normotension].

In order to evaluate circadian blood-pressure (BP) profile characteristics typical of old age, we compared circadian BP profile in elderly subjects with isolated systolic hypertension (ISH; greater than 160/less than 90 mmHg), essential hypertension (EH; diastolic BP greater than or equal to 95 mmHg), and normotension (N; less than 140/less than 90 mmHg). Each group consisted of 18 subjects, approximately matched in age and sex, (age range 60-82 years; mean age 67.5 years). Ambulatory 24-h BP-monitoring was carried out using a SpaceLabs 90202 with measurements made every 30 min. In ISH, causal systolic BP is higher and circadian systolic BP is lower than in EH (n.s.). Circadian diastolic BP is lower than in EH and higher than in N; both are statistically highly significant (p less than 0.001, u-test, Wilcoxon). The decrease during the resting period is 6 mmHg in EH and 17 mmHg in ISH. In ISH there is a considerable difference of 39 mmHg between casual BP and circadian 24-h BP, in contrast to N and to EH, and this is due to a particular hyperreactivity. This discrepancy is typical of old age and holds the danger of over-treatment, if only causal BP is taken into consideration.

Aged↗
PubMed1992

[Changes in systemic fibrinolysis and blood coagulation parameters in local thrombolysis with tissue plasminogen activator (rt-PA)].

During the local fibrinolysis with rt-PA (2.5 mg/h) systemic plasminogen and alpha 2-antiplasmin activities slightly decrease, but the fibrinolytic system is compensated during the whole treatment. The d-dimer plasma levels increase dependently on the mass of thrombus. Despite the administration of high doses of heparin during the fibrinolysis thrombin is formed, measured as thrombin-antithrombin III complex (TAT).

Blood Coagulation↗
PubMed1991

[Appendicitis in early childhood].

Between 1982 and 1987 550 appendectomies in children under sixteen years of age were carried out in our surgical department. Only 21 patients were children under 4 years of age, accounting for 4% of all patients. The perforation rate however, was 44% in contrast to 12% in older children. One reason is the more difficult, und therefore often delayed, diagnosis. The mean duration of symptoms of appendicitis in young children was 3.4 days. In the special case of perforated appendicitis the mean duration of symptoms was 132 hours, as compared with 42 hours in children without perforation. Clinical examination is decisive for the diagnosis. Fever and vomiting are non-specific symptoms, but frequently present. Some 81% of the patients had leukocytosis over 15,000. If there are any doubts about the indication for appendectomy, x-ray examination should be carried out as a further useful diagnostic procedure.

Appendectomy↗
PubMed1991

[Shoulder girdle injury in childhood. Operation or conservative procedure?].

The fracture of the clavicle is a very frequent injury to children and young adults. Using a figure-of-eight bandage for treatment leads to good functional result and acceptable cosmetical appearance. Indications for an open reduction are rare: they are confined to brachial plexus lesions, injuries to the subclavian vessels, open fractures or fractures of the outer third of the clavicle combined with an acromioclavicular separation. Fractures of the scapula merely require immobilization and subsequent physiotherapy to yield satisfactory results. Distorsions and subluxations of the joints of the clavicle are to be managed conservatively, too. Only in cases of complete ruptures of the acromioclavicular, coracoclavicular or sternoclavicular ligaments, it is necessary to perform an open reduction and repair of the ligaments.

Acromioclavicular Joint↗
PubMed1991

In vitro genotoxicity of dimethyl terephthalate.

Dimethyl terephthalate (DMTP), the para configuration of dimethyl phthalate, is one of the basic monomers used in the synthesis of polyethylene terephthalate (PET) plastics. Human exposure to DMTP may primarily occur during the manufacture of PET fibers and films. The mutagenic potential of dimethyl terephthalate was evaluated using a battery of in vitro short-term tests: the Ames test; DNA single-strand break assays in CO60 cells and in primary rat hepatocytes; UDS in HeLa cells; chromosome aberration and micronucleus assays in human peripheral blood lymphocytes; selective DNA amplification in CO60 and in Syrian hamster embryo cells. The results of this battery of in vitro assays clearly show that DMTP is nongenotoxic. By contrast, other authors have found DMTP to be an in vivo clastogenic compound and suggested that the mechanisms involved in these in vivo effects seem to have nothing in common with genotoxicity and are still unknown.

Adult↗
PubMed1991

Electrophilic gamma-lactone kappa-opioid receptor probes. Analogues of 2'-hydroxy-2-tetrahydrofurfuryl-5,9-dimethyl-6,7-benzomorphan diastereomers.

Benzomorphans with an electrophilic group in the nitrogen substituent were prepared as potentially irreversible ligands for the kappa-opioid receptor. These were synthesized from products of the reaction of normetazocine with the enantiomers of 5-(iodomethyl)-gamma-butyrolactone (11). alpha-Methylene gamma-lactones 5 and 7 and endocyclic alpha,beta-unsaturated gamma-lactones 8 and 9 were prepared from the corresponding saturated gamma-lactones 13 and 23 possessing the "active" (1R,5R,9R)-benzomorphan stereochemistry. Only gamma-lactones 8, 9, 13, and 23, lacking the exocyclic methylene group, retain significant affinities for opioid receptor binding sites when compared with the reference compounds (2"S)-3 and (2"R)-3. As observed with these references compounds, greater binding affinity is also seen with gamma-lactone diastereomers having the 2"S stereochemistry in the nitrogen substituent. Although the gamma-lactones do not bind irreversibly in opioid receptor preparations, they do show kappa-receptor selectivities comparable to those observed for the reference compounds.

Animals↗
PubMed1991

Short-term and long-term problems after duraplastic enlargement of anterior abdominal wall.

Between 1974 and 1989, 49 out of 83 children with gastroschisis or omphalocele underwent duraplastic enlargement of the anterior abdominal wall. The solvent dried dura proved to be the most useful material, which could be left in place even after a scar had formed. Abdominal complications depend on preexisting damage of the intestine and on the intraabdominal pressure resulting from closure. Long-term disturbances of the gastrointestinal and abdominal wall function are comparable to the results of other reconstructive methods.

Abdominal Muscles↗
PubMed1991

Corneal immune ring as a complication of soft extended wear contact lens use.

Corneal immune ring (CIR) appeared in the eyes of three patients who wore their extended wear contact lenses while sleeping. CIR's have not been reported as a complication associated with the wear of soft extended wear lenses. The CIR appeared within days of an episode of ulcerative keratitis with an infiltrative component. Treatment with topical antibiotic and anti-inflammatory agents produced resolution of the corneal lesions. The clinical appearance of the lesions as well as the time frame involved suggest that the immune response that produced the CIR was triggered by bacterial endotoxin through the properdin-mediated complement pathway.

Adult↗
PubMed1991

[Skin culture on the burn wound as a final skin replacement].

The epithelium-specific nutritive solution initially developed for laboratory use by Parshley and Simms allows the culture of autologous epithelium on a burn wound. The basal cell layer of the wound is encouraged to proliferate strongly if the fresh wound is kept moist until the time of epithelial transfer on about the 10th day. Both mechanisms-growing skin on the wound an proliferation of the wound edges-lead to quick an painless wound healing. Histological, and particularly autohistoradiographical findings confirm these statements. Slides of clinical cases show the island-like growth of epithelium on the wound and the cosmetic result.

Burns↗
PubMed1991

Outcome and cost analysis of scheduled versus emergency scleral buckling surgery.

Conventional wisdom holds that a retinal detachment of recent onset should be regarded as a surgical emergency. A delay in surgery may result in an extension of detachment for patients with an attached macula and a worse visual outcome for patients with a detached macula. However, the potential disadvantages of performing surgery on an emergency basis must be weighed against the risks of delaying surgery; disadvantages include a greater frequency of operative complications resulting from fatigue factors among the operating personnel, an increased anesthetic risk due to inadequate time to assess and stabilize coexisting medical problems, and higher hospital costs. In this retrospective study covering 4 1/2 years, we compared the risks, benefits, length of hospitalization, and costs of scleral buckling surgery for retinal detachments performed as an emergency procedure or on the day following admission. After a 15% random selection from 884 consecutive operations, 48 emergency procedures were compared with 89 scheduled procedures. Patients selected for emergency surgery had better visual prognoses than scheduled patients. The potential for risk of systemic complications was not a reason for postponing surgery. None of the 18 patients with an attached macula experienced macular involvement while awaiting scheduled surgery. There were no differences between emergency and scheduled patients in ocular or systemic complications, rate of reattachment, rate of decreased visual acuity following surgery, visual outcome adjusted for prognosis, or, since 1985, length of hospital stay. Cost was greater for patients having emergency surgery, because of a difference in pay scales for support personnel.

Cost-Benefit Analysis↗