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Biomedical subjects

S Stahl

Publications and source records attributed to S Stahl.

At least 73 records · Page 4Linked to original sources
PubMed1997

The role of laminin-5 and its receptors in mammary epithelial cell branching morphogenesis.

In vivo, normal mammary epithelial cells utilize hemidesmosome attachment devices to adhere to stroma. However, analyses of a potential role for hemidesmosomes and their components in mammary epithelial tissue morphogenesis have never been attempted. MCF-10A cells are a spontaneously immortalized line derived from mammary epithelium and possess a number of characteristics of normal mammary epithelial cells including expression of hemidesmosomal associated proteins such as the two bullous pemphigoid antigens, alpha 6 beta 4 integrin and its ligand laminin-5. More importantly, MCF-10A cells readily assemble mature hemidesmosomes when plated onto uncoated substrates. When maintained on matrigel, like their normal breast epithelial cell counterparts, MCF-10A cells undergo a branching morphogenesis and assemble hemidesmosomes at sites of cell-matrigel interaction. Function blocking antibodies specific for human laminin-5 and the alpha subunits of its two known receptors (alpha 3 beta 1 and alpha 6 beta 4 integrin) not only inhibit hemidesmosome assembly by MCF-10A cells but also impede branching morphogenesis induced by matrigel. Our results imply that the hemidesmosome, in particular those subunits comprising its laminin-5/integrin 'backbone', play an important role in morphogenetic events. We discuss these results in light of recent evidence that hemidesmosomes are sites involved in signal transduction.

Antibodies↗
PubMed1997

The effect of local infiltration with morphine before carpal tunnel release.

We compared the effect of infiltration with a mixture of 1 per cent lidocaine and two milligrams of morphine in twenty-five patients who were to be managed with a carpal tunnel release with the effect of infiltration with 1 per cent lidocaine only in a second group of twenty-five patients who were to have such a release. In both groups, the injection was administered after inflation of the tourniquet. During the procedure, the patients' movement and vocalization of discomfort did not differ substantially between the groups. However, in the immediate postoperative period, the patients who had received morphine indicated a significantly higher score (on a visual-analog scale) for peak intraoperative pain than did the patients who had received lidocaine only (2.44 +/- 1.73 points compared with 1.32 +/- 1.22 points; p = 0.01). The numbers of patients who had pain in the recovery room, the numbers of patients who received analgesics in the recovery room, and the scores for pain at the time of discharge were similar for the two groups. The score for pain on the first postoperative day was more than 4 points for seven patients who had received morphine, whereas no patient who had received lidocaine only had a score of more than 4 points (p = 0.01); however, the amount of analgesics taken at home was similar for the two groups. Postoperative complications, which included hypotension, fainting, weakness, and chest pain, occurred in eight patients (32 per cent) who had received morphine and in none who had received lidocaine only (p < 0.01).

Adult↗
PubMed1997

The efficacy of an injection of steroids for medial epicondylitis. A prospective study of sixty elbows.

We report the details of a prospective, randomized, double-blind study that was undertaken to analyze the short-term and long-term effects of the local injection of methylprednisolone to treat medial epicondylitis. Fifty-eight patients (sixty elbows) were assigned to receive a single injection of 1 per cent lidocaine with either forty milligrams of methylprednisolone (experimental group) or saline solution (control group); both groups were also managed with physical therapy and the use of non-steroidal anti-inflammatory drugs. The two groups were not significantly different with regard to the age and gender of the patients, the duration of the symptoms, the degree of pain before the injection, or the number of dominant upper limbs involved. Six weeks after the injection, the experimental group had significantly less pain than the control group (p < 0.03), as determined with a modification of the grading system of Nirschl and Pettrone. However, the groups did not differ with regard to pain at three months and at one year. The intensity of pain, as measured on a visual-analog scale, did not differ between the two groups six weeks and one year after the injection. We believe that the improvement observed in both groups primarily reflects the natural history of the disorder, and we conclude that the local injection of steroids provides only short-term benefits in the treatment of medial epicondylitis.

Adult↗
PubMed1997

Human gene therapy for melanoma: CT-guided interstitial injection.

OBJECTIVE: Our intent is to describe the role of CT in the intratumoral injection of Allovectin-7 (Vical, San Diego, CA), an allogeneic class I major histocompatibility complex antigen, HLA-B7, formulated with cationic lipid, in the treatment of metastatic malignant melanoma. MATERIALS AND METHODS: Ten patients with metastatic malignant melanoma were treated with gene therapy in which we used CT-guided intratumoral injection of plasmid DNA containing the HLA-B7 gene. This therapy was part of a phase I gene therapy trial in patients with metastatic melanoma. CT guidance was chosen as an accurate way to direct gene delivery in patients with deep, impalpable lesions. Tumor locations included pulmonary, mediastinal, hepatic, adrenal, and paracaval sites. Patients in the CT protocol underwent baseline CT studies. Examinations were repeated 2, 4, and 8 weeks after gene therapy and thereafter at 3-month intervals. Both injected and noninjected tumors were measured. CT-guided injections of 10, 50, or 250 micrograms of plasmid DNA were performed with 22-gauge spinal needles. Injection volumes were between 1.0 and 4.0 ml, depending on tumor size. CT-guided core biopsy specimens were obtained (with 18- or 20-gauge needles) from the selected tumor before therapy and 2, 4, and 8 weeks after therapy to assess HLA-B7 plasmid DNA and gene expression. Peripheral blood was analyzed for cytotoxic T lymphocytes directed against HLA-B7. RESULTS: CT-guided intratumoral injections were successful in delivering genetic material to all patients with impalpable tumors. Significant responses (as defined by a decrease of 25% or more in the product of the length and width of the injected tumor) were observed in six of the 10 patients. One of these six patients who had a solitary lesion remains free of disease 19 months after gene therapy. HLA-B7 protein expression was detected in 89% of biopsy specimens, and plasmid DNA and messenger RNA were detected in 56% and 22% of biopsy specimens, respectively. CONCLUSION: CT provides a safe, accurate, and efficacious way to monitor and assess tumor progression and response, and it provides guidance for biopsies and intratumoral injections during gene therapy. Significant responses in injected tumors of six of the 10 patients in our study suggest that further clinical trials of this gene therapy are warranted.

Adult↗
PubMed1996

[Conservative therapy in carpal tunnel syndrome].

A prospective study was designed to determine which patients with carpal tunnel would respond to conservative therapy (splinting and local injection of corticosteroids). The study included 50 hands of 34 patients, aged 25-80 years, with a mean follow-up of 18 months. Conservative therapy was effective in 82% of hands after 8 weeks, but symptoms subsequently recurred, so that by the end of a year only 20% remained asymptomatic. Failure of conservative therapy was predicted by long duration of symptoms, older age, permanent paresthesia, 2-point discrimination threshold above 6 mm, positive Phalen test within 30 seconds, and long motor and sensory distal latency.

Adrenal Cortex Hormones↗
PubMed1996

[Impingement syndrome following direct injuries of the shoulder joint].

Impingement is the most common cause of pain and limitation of movement in the shoulder, with painful arc syndrome its major clinical sign. It usually becomes manifest at between 70 degrees-120 degrees of abduction, but in severe cases, this may be reduced to only 50 degrees-70 degrees. We studied 22 patients who had developed shoulder impingement following direct injuries and who had been treated by anterior acromioplasty and decompression, with an average follow-up of 32 months. 5 had sustained fractures of the greater tuberosity of the humerus at the time of injury, 14 had tears of the rotator cuff of various sizes (1 in both shoulders) and 3 had developed fibrotic scars of the subacromial bursa. Excellent or good results were achieved in 86.6%. Healing time was shorter, and there was return of full range of shoulder movement in those with subacromial scars, undisplaced fractures of the greater tuberosity, or those with a small tear of the rotator cuff. Recovery took longer in those with larger tears of the rotator cuff and in those with displaced fractures of the greater tuberosity. Recovery time was proportional to the size of the rotator cuff tear. It is concluded that direct trauma to the shoulder bears a direct relationship to the development of impingement syndrome, and that at surgery a concomitant tear in the rotator cuff is seen more than 2/3. Because of the high rate of success in surgical treatment of this syndrome, operation is indicated when a few months of physical therapy and analgesics fail to provide relief. In the presence of fractures, decompression surgery should be postponed until the fracture has united.

Acromion↗
PubMed1996

Anisotropic rotational diffusion of perdeuterated HIV protease from 15N NMR relaxation measurements at two magnetic fields.

15N NMR relaxation times in perdeuterated HIV-1 protease, complexed with the sub-nanomolar inhibitor DMP323, have been measured at 600 and 360 MHz 1H frequency. The relative magnitudes of the principal components of the inertia tensor, calculated from the X-ray coordinates of the protein-drug complex, are 1.0:0.85:0.44. The relation between the T1/T2 ratios observed for the individual backbone amides and their N-H orientation within the 3D structure of the protease dimer yields a rotational diffusion tensor oriented nearly collinear to the inertia tensor. The relative magnitudes of its principal components (1.00:1.11:1.42) are also in good agreement with hydrodynamic modeling results. The orientation and magnitude of the diffusion tensors derived from relaxation data obtained at 360 and 600 MHz are nearly identical. The anisotropic nature of the rotational diffusion has little influence on the order parameters derived from the 15N T1 and T2 relaxation times; however, if anisotropy is ignored, this can result in erroneous identification of either exchange broadening or internal motions on a nanosecond time scale. The average ratio of the T1 values measured at 360 and 600 MHz is 0.50 +/- 0.015, which is slightly larger than the value of 0.466 expected for an isotropic rigid rotor with tau c = 10.7 ns. The average ratio of the T2 values measured at 360 and 600 MHz is 1.14 +/- 0.04, which is also slightly larger than the expected ratio of 1.11. This magnetic field dependence of the T1 and T2 relaxation times suggests that the spectral density contribution from fast internal motions is not negligible, and that the chemical shift anisotropy of peptide backbone amides, on average, is larger than the 160 ppm value commonly used in 15N relaxation studies of proteins.

Anisotropy↗
PubMed1996

Carpal tunnel syndrome in pregnancy: indications for early surgery.

The incidence of carpal tunnel syndrome is increased during pregnancy. The common conventional therapeutic approach is conservative, as symptoms usually abate after delivery. We describe our experience with 65 hands (50 patients), who were treated initially by a conservative approach and later, when required, surgically. We found that all patients who (i) had either started having CTS symptoms during the first two trimesters or had previous history of CTS symptoms; and (ii) had both a positive Phalen test within less than 30 seconds and abnormal two point discrimination at the finger tips ( > 6 mm), were eventually operated upon, either during or after pregnancy, as conservative measures failed. We therefore recommend consideration of an early surgical approach in patients fulfilling these criteria.

Adult↗
PubMed1996

Closure of wounds in the upper extremity using a skin stretching device.

A skin stretching device (SSD) harnessing the viscoelastic properties of skin using incremental traction has been used in 20 patients with skin deficits in the upper extremity. Complications were few considering the extensive damage to the skin and included slight partial dehiscence, necrosis of skin edges, local infection and hypertrophic scars. All wounds healed without the need for further surgical procedures. Application of the SSD is simple and it can even be used at the bedside under local anaesthesia. It reduces the need for more complicated surgical procedures like grafts or flaps.

Adult↗
PubMed1996

The combination of morphine with local anaesthetic in rhinoplasty--no evidence of a peripheral morphine effect.

BACKGROUND: The recognition of a peripheral opioid action has prompted a number of clinical reports demonstrating a prolonged analgesic effect of peripheral opiate. As most studies have used a model of intraarticular instillation of narcotic we examined direct morphine infiltration of the surgical site in a unique clinical model. METHODS: Sixty patients undergoing primary rhinoplasty were entered into this prospective, randomized, double-blind study. Patients received a standard protocol of premedication, intravenous sedation, and nasal block. Two 2 ml syringes containing saline or morphine 3 mg in saline were provided for IM injection and for addition to the local anesthetic (IW, intrawound): Group I (control)-saline IW, saline IM; Group II morphine IW, saline IM; Group III-saline IW, morphine IM. Intraoperative assessments included need for further sedation, need for further local anesthetic, and degree of bleeding. Recovery room analgesic requirements, pain scores, and recall of intraoperative pain were recorded prior to discharge. Followup phone calls at 24 hours recorded home pain scores and analgesic use during the first postoperative day. RESULTS: Significantly more patients in Group II (9/20) required supplemental local anesthetic intraoperatively compared to Group I (2/20) and Group III (0/20). Significantly more patients in Group II (6/20) recalled their surgical experience as painful compared to Group I (1/20) and Group III (1/20). Group II patients also evidenced significantly more operative bleeding. There were no differences in postoperative pain scores, but Group I patients required analgesic in the recovery room significantly more than in Groups II and III (85% vs 45% and 50%, respectively). There were no differences between groups in analgesic consumption at home. CONCLUSIONS: The results of this study indicate that the preoperative injection of intrawound morphine in combination with the local anesthetic both promotes bleeding and has an early pain-enhancing effect while providing no late analgesic benefit beyond that of IM morphine.

Adult↗
PubMed1995

Transfer of the human glucocerebrosidase gene into hematopoietic stem cells of nonablated recipients: successful engraftment and long-term expression of the transgene.

In trying to develop methods of gene therapy for Gaucher disease that will avoid the morbidity and mortality associated with bone marrow (BM) ablation, we transplanted BM stem cells transduced with a retroviral vector containing the human glucocerebrosidase cDNA into normal, nonablated, syngeneic mice. Donor BM from untreated male mice or treated with 5-fluorouracil (5-FU) was transduced ex vivo using a standard 4-day transduction protocol. Recipient female mice were injected one time only or once daily for 5 consecutive days or once a week for 5 consecutive weeks using 2 x 10(7) (untreated BM) or 2 x 10(6) (5-FU-treated BM) cells per injection. Initial transduction efficiency into colony-forming unit-spleen (CFU-S) was 80% to 100%. Recipient analysis was performed at least 6 months after the last transplantation. The best engraftment of donor stem cells, up to 5% by secondary CFU-S analysis, was obtained with multiple injections of transduced BM not previously treated with 5-FU. Polymerase chain reaction (PCR) amplification for both the transgene and the Y chromosome identified the progeny of transduced stem cells in various hematopoietic and non-hematopoietic organs. The copy number of the transgene in stem cells was 0.13 to 2.8. Transgene expression was shown by reverse transcriptase-PCR, in situ hybridization, and immunohistochemistry. No serious side effects of the procedure were noted. We conclude that multiple transplants of retrovirally transduced BM cells into nonablated recipients may be a safe and effective therapeutic modality for a number of genetic hematopoietic disorders.

Animals↗
PubMed1995

Immunogens containing sequences from antigen Pf332 induce Plasmodium falciparum-reactive antibodies which inhibit parasite growth but not cytoadherence.

Immunogens based upon sequences from the P. falciparum asexual blood stage antigen Pf332 were assessed for their capacity to induce antibodies inhibiting parasite growth or cytoadherence of infected erythrocytes in vitro. Selection of the Pf332 sequences was based on their reactivity with the human monoclonal antibody (MoAb) 33G2 which inhibits parasite growth as well as cytoadherence in vitro. Octameric multiple antigen peptides (MAP) were assembled based upon either a trimer of the minimal epitope recognized by the MoAb, VTEEI, or a Pf332 sequence including that motif, SVTEEIAEEDK. A dimer of SVTEEIAEEDK was also expressed in Escherichia coli, genetically fused to ZZ, two IgG-binding domains of staphylococcal protein A. Rabbit antibodies elicited by the immunogens reacted with Pf332 in immunofluorescence and in ELISA with Pf332 peptides which were also recognized by MoAb 33G2. The MAP with branched (VTEEI)3 peptide induced the highest titres of P. falciparum-reactive antibodies. In contrast to MoAB 33G2, none of the polyclonal Pf332 reactive sera cross-reacted with repeat sequences of the malaria antigen Pf155/RESA. The polyclonal Pf332-reactive antibodies inhibited parasite growth efficiently but had no or very low inhibitory effect in a cytoadherence assay. Thus, while Pf332 may be an important target for parasite neutralizing antibodies its involvement in cytoadherence is unclear.

Amino Acid Sequence↗
PubMed1995

Retaining cocaine-abusing women in a therapeutic community: the effect of a child live-in program.

A clinical trial examined whether retention of cocaine-abusing women in a therapeutic community can be improved by permitting their children to live with them during treatment. Fifty-three women were randomly assigned to either the standard community condition (n = 22), in which children were placed with the best available caretaker, or the demonstration condition (n = 31), in which one or two of the children lived with their mother in the community. Survival analysis distributions indicated that demonstration women remained in treatment significantly longer than standard treatment women. (Mean length of stay was 300.4 days vs 101.9 days, respectively.)

Adult↗
PubMed1995

Transvaginal sonographic diagnosis of fetal finger abnormalities in early gestation.

The prenatal sonographic diagnosis of fetal finger abnormalities was recorded in a study population of 20,000 pregnant patients. All scans were performed with a vaginal transducer at 13 to 17 weeks' gestation. The following abnormalities were observed: six cases of polydactyly, three of syndactyly, nine cases of overlapping fingers, two cases of cleft hands, two cases of adactyly, one case of aphalangia, and one case of clasped thumb. In 15 of the 25 fetuses with finger abnormalities, we observed associated malformations or chromosomal disorders, or both. We therefore recommend that examination of the fingers and hands should become an integral part of the early ultrasonographic evaluation of the fetus.

Chromosome Aberrations↗