Biomedical subjects

M S Shapiro

Publications and source records attributed to M S Shapiro.

At least 37 records · Page 2Linked to original sources

PubMed1997

A biomechanical study of replacement of the posterior cruciate ligament with a graft. Part 1: Isometry, pre-tension of the graft, and anterior-posterior laxity.

UNLABELLED: Twelve fresh-frozen knee specimens from cadavera were subjected to anterior-posterior laxity testing with 200 newtons of force applied to the tibia; testing was performed before and after a femoral load-cell was connected to a mechanically isolated cylindrical cap of subchondral femoral bone containing the femoral origin of the posterior cruciate ligament. The posterior cruciate ligament then was removed, the proximal end of a thin trial isometer wire was attached to one of four points designated on the femur, and displacement of the distal end of the wire relative to the tibia was measured over a 120-degree range of motion. The potted end of a ten-millimeter-wide bone-patellar ligament-bone graft was centered over the femoral origin of the ligament and attached to the femoral load-cell. Isometry measurements were repeated with the wire attached to the bone block of the free end of the graft in the tibial tunnel. Force was recorded at the load-cell (representing force in the intra-articular portion of the graft) as pre-tension was applied, with use of a calibrated spring-scale, to the tibial end of the graft. A laxity-matched pre-tension of the graft was determined such that the anterior-posterior laxity of the reconstructed knee at 90 degrees of flexion was within one millimeter of the laxity that was measured after installation of the load-cell. Anterior-posterior testing was repeated after insertion of the graft at the laxity-matched pre-tension. The least amount of change in the relative displacement of the trial wire over the 120-degree range of flexion occurred when the wire was attached to the proximal point on the femur (a point on the proximal margin of the femoral origin of the posterior cruciate ligament, midway between the anterior and posterior borders of the ligament). The greatest change in the relative displacement was associated with the anterior point (a point on the anterior margin of the femoral origin of the ligament, midway between the proximal and distal borders). The mean relative displacements of the trial wire when it was attached to a point at the center of the femoral origin of the ligament were not significantly different from the corresponding mean displacements of the distal end of the graft when the proximal end of the graft was centered at this point. At 90 degrees of flexion, the force recorded by the load-cell averaged 64 to 74 per cent of the force applied to the tibial end of the graft. The laxity-matched pre-tension of the graft at 90 degrees of flexion (as recorded by the load-cell) ranged from six to 100 newtons (mean and standard deviation, 43.0 +/- 33.4 newtons). With the numbers available, the mean laxities after insertion of the graft were not significantly different, at any angle of flexion, from the corresponding mean values after installation of the load-cell. CLINICAL RELEVANCE: Isometer readings from a trial wire attached to a point on the femur provided an accurate indication of the change in the length of a graft subsequently centered at that point. Anteriorly placed femoral tunnels should be avoided, as the isometer readings indicated increased tension, with flexion of the knee, in a graft placed in this region. The force in the intra-articular portion of the graft was always less than the force applied to the bone block in the tibial tunnel. Therefore, the femoral end of the graft should be tensioned to avoid frictional losses from the severe bend in the graft as it passes over the posterior tibial plateau. With correct pre-tensioning of a graft, normal anterior-posterior laxity at 0 to 90 degrees of flexion can be restored. However, because of the considerable range in the laxity-matched pre-tensions, we recommend that the pre-tension be greater than forty-three newtons for all patients to ensure that normal laxity is restored.

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PubMed1997

A biomechanical study of replacement of the posterior cruciate ligament with a graft. Part II: Forces in the graft compared with forces in the intact ligament.

UNLABELLED: A femoral load-cell was installed in twelve fresh-frozen knee specimens from cadavera, to measure the resultant force at the femoral origin of the posterior cruciate ligament during a series of tibial-loading tests. The posterior cruciate ligament was removed, and a ten-millimeter-wide bone-patellar ligament-bone graft was inserted. The knee was flexed to 90 degrees, the graft was pre-tensioned to restore the anterior-posterior laxity to that recorded after installation of the load-cell, and the loading tests were repeated. With the tibia locked in neutral rotation and a 200-newton posterior force applied to the tibia, the mean force generated in the intact posterior cruciate ligament ranged from 220 newtons at 90 degrees of flexion to thirty-six newtons at full extension. When the tibia was locked in external rotation during the posterior drawer test, the force was reduced when the knee was flexed 10 to 70 degrees; when the tibia was locked in internal rotation, the mean force was reduced at only 30 and 45 degrees of flexion. The mean forces in the graft were not significantly different, with the numbers available, from the corresponding values for the intact ligament during application of a straight posterior tibial force (neutral tibial rotation), during application of a fifteen-newton-meter flexion or extension moment (hyperflexion or hyperextension), during application of a ten-newton-meter varus or valgus moment, or during application of a ten-newton-meter internal or external tibial torque. With the numbers available, there were no significant differences between the mean tibial rotations associated with the intact posterior cruciate ligament and those associated with the graft at any angle of flexion, without or with applied tibial torque. CLINICAL RELEVANCE: The amount of force generated in the posterior cruciate ligament during the posterior drawer test depends on the angle of flexion at which the test is performed. When the angle of flexion is near 90 degrees, all of the posterior force applied to the tibia is transmitted to the ligament and the force in the ligament is not affected by the position of tibial rotation. When the test is performed at an angle of flexion near 30 degrees and in neutral tibial rotation, other structures (such as the collateral ligaments and the posterior part of the capsule) help to resist the posterior force applied to the tibia. The position of tibial rotation is important when the test is performed with the knee at an angle of flexion near 30 degrees, as secondary structures pre-tensioned by tibial torque act to reduce the amount of force carried by the posterior cruciate ligament even more. With a few minor exceptions, we found that the forces in a graft used to replace the posterior cruciate ligament were approximately the same as those in the intact ligament. Therefore, there appears to be little justification for restricting low-level rehabilitation activities once the fixation of the graft has healed. However, forces in the graft could be quite high during hyperextension and hypertension, as they are in the intact ligament. Thus, bracing in the early postoperative period may be advisable to prevent these motions.

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PubMed1997

Voluntary scapulothoracic subluxation: a case report.

Dislocation of the scapula is a rare event, usually associated with massive trauma and injury. We report a case of a patient for whom dislocation was the sole presentation. The possibility of voluntary dislocation for secondary gain was suspected, but because of perceived progressive brachial plexus involvement, urgent closed reduction was undertaken and led to resolution of the neurologic symptoms. The patient returned 1 year later with similar complaints and findings, but declined another closed reduction attempt when offered only an interscalene regional block as pain relief. The diagnosis of voluntary dislocation should be considered in a patient presenting with superior and lateral migration of the scapula, without a history of trauma.

Adult↗

PubMed1996

Pseudohypoparathyroidism type Ia: two new heterozygous frameshift mutations in exons 5 and 10 of the Gs alpha gene.

Pseudohypoparathyroidism type Ia (PHP-Ia) is a hereditary disease characterized by resistance to PTH and other hormones that act via cAMP. Patients have deficient activity of Gs alpha, the alpha subunit of the G protein, which couples hormone receptors to stimulation of adenylate cyclase. We describe two new mutations discovered in two sporadic patients with PHP-Ia. Using genomic DNA, we have amplified exons 2-13 of the Gs alpha gene (GNAS1) by PCR, and sequenced the resulting products. Both patients had Albright's hereditary osteodystrophy, resistance to multiple hormones, and deficient Gs alpha activity. In the first patient, a deletion of a C in exon 5 at codon 115 was found. In the second patient, an insertion of a C in exon 10 at codon 267 was detected. Both these heterozygous mutations cause frameshift, and predict decreased production of Gs alpha. This report adds two new Gs alpha mutations to the known ten mutations recently described.

Adolescent↗

PubMed1996

Delayed reduction of traumatic knee dislocation. A case report and literature review.

Knee dislocation after high energy trauma poses a major challenge to patients and treating physicians. The case presented documents the history and treatment of an unreduced posterior knee dislocation discovered 24 weeks after injury. Delayed surgical reduction was achieved, and satisfactory results were obtained with 22 months of followup of the patient. A detailed review of the literature found no comparable examples of longstanding traumatic dislocations of the knee but shed light on the probable cause for this unusual case. Close clinical followup, even after appropriate initial treatment of knee dislocations, is needed to eliminate similar occurrences.

Adolescent↗

PubMed1996

Selective disruption by protein kinases of G-protein-mediated Ca2+ channel modulation.

1. We studied the effects of phorbol-12-myristate, 13-acetate (PMA) on G-protein-mediated inhibition of Ca2+ channels by several neurotransmitters in rat superior cervical ganglion (SCG) sympathetic neurons, with the use of the whole cell patch clamp. PMA attenuated membrane-delimited inhibition of calcium currents (ICa) by norepinephrine (NE) and somatostatin by more than half, but did not attenuate inhibition by M1 muscarinic receptors, which use a diffusible cytoplasmic messenger. Inhibition of ICa by NE through pertussis-toxin-sensitive and -insensitive G proteins was equally attenuated by PMA. PMA enhanced ICa in about half the neurons (enhancement of 10 +/- 1%, mean +/- SE) and strongly reduced the holding current in 44 of 61 cells. 2. The M-type K+ current (IM) was not suppressed by PMA, and PMA did not attenuate inhibition of IM by muscarinic agonists, which is also via a diffusible cytoplasmic messenger. 3. Attenuation of NE and somatostatin inhibition by PMA was blocked by 1 microM staurosporine, a broad-spectrum protein kinase inhibitor. Tests with three inhibitors selective for distinct isoforms of protein kinase C (PKC) gave mixed results. PMA's actions were unaffected by 1 microM calphostin C, blocked by 500 nM bisindolylmaleimide, and unaffected by the pseudosubstrate inhibitor PKC19-36. 4. Thus we find that two membrane-delimited signaling pathways that inhibit ion channels in rat SCG neurons are strongly attenuated by PMA, but signaling pathway(s) that use a diffusible cytoplasmic messenger are not. We speculate that a nonstandard PKC isoform, perhaps PKC mu, mediates PMA actions.

Animals↗

PubMed1996

Genetic homogeneity of autoimmune polyglandular disease type I.

Autoimmune polyglandular disease type I (APECED) is an autosomal recessive autoimmune disease (MIM 240300) characterized by hypoparathyroidism, primary adrenocortical failure, and chronic mucocutaneous candidiasis. The disease is highly prevalent in two isolated populations, the Finnish population and the Iranian Jewish one. Sporadic cases have been identified in many other countries, including almost all European countries. The APECED locus has previously been assigned to chromosome 21q22.3 by linkage analyses in 14 Finnish families. Locus heterogeneity is a highly relevant question in this disease affecting multiple tissues and with great phenotypic diversity. To solve this matter, we performed linkage and haplotype analyses on APECED families rising from different populations. Six microsatellite markers on the critical chromosomal region of 2.6 cM on 21q22.3 were analyzed. Pairwise linkage analyses revealed significant LOD scores for all these markers, maximum LOD score being 10.23. The obtained haplotype data and the geographic distribution of the great-grandparents of the Finnish APECED patients suggest the presence of one major, relatively old mutation responsible for approximately 90% of the Finnish cases. Similar evidence for one founder mutation was also found in analyses of Iranian Jewish APECED haplotypes. These haplotypes, however, differed totally from the Finnish ones. The linkage analyses in 21 non-Finnish APECED families originating from several European countries provided independent evidence for linkage to the same chromosomal region on 21q22.3 and revealed no evidence for locus heterogeneity. The haplotype analyses of APECED chromosomes suggest that in different populations APECED is due to a spectrum of mutations in a still unknown gene on chromosome 21.

Alleles↗

PubMed1995

Multiple G-protein-coupled pathways inhibit N-type Ca channels of neurons.

Muscarinic receptors depress Ca2+ currents in superior cervical ganglion neurons by two signaling pathways. One is sensitive to pertussis toxin and acts rapidly by a membrane-delimited pathway on the channels. The other is not sensitive to pertussis toxin and acts more slowly through an unknown second messenger. These pathways are shared with several other agonists.

Alkaloids↗

PubMed1995

Pancreatic polypeptide inhibits calcium channels in rat sympathetic neurons via two signaling pathways.

1. We studied modulation of N-type Ca2+ channels in adult rat superior cervical ganglion (SCG) neurons by pancreatic polypeptide (PP) using whole cell clamp. In large (> 20 pF) SCG neurons, PP inhibited ICa (35 +/- 2%, mean +/- SE) in a concentration-dependent fashion, with one-half maximal inhibition at 19 nM. 2. One-third of the inhibition was blocked by pertussis toxin, about one-half was blocked by N-ethylmaleimide (NEM) treatments, and about one-half was voltage dependent. The NEM-insensitive component of the PP inhibition was voltage independent and not significantly blocked by intracellular Ca2+ chelators. 3. The NEM-insensitive component was only weakly attenuated by GDP-beta-S, and moderately reversible with guanosine 5'-triphosphate (GTP)-gamma-S, in the whole cell pipette, leaving open the possibility that it is not mediated by a G protein. 4. Hence, PP inhibits ICa via two mechanisms: one G-protein-mediated and the other possibly G-protein independent. The former pathway is sensitive to pertussis toxin (PTX) and NEM, voltage dependent, and shared by several other transmitters in these cells. The latter pathway is PTX-and NEM-insensitive, not voltage dependent, and not affected by the presence of intracellular Ca2+ chelators.

Adrenergic Fibers↗

PubMed1995

Pellegrini-Stieda syndrome.

The Pellegrini-Stieda "sign" is commonly seen in patients who have a history of trauma to the medial collateral ligament of the knee. Although most are asymptomatic, a few patients will develop the characteristic Pellegrini-Stieda syndrome, which can be severely limiting. When conservative measures fail, surgical treatment consisting of excision of the bony fragment with careful repair of the medial collateral ligament can eradicate the symptoms. This syndrome is reviewed in detail, and an illustrative case report is included.

Accidents, Traffic↗

PubMed1994

Angiotensin II inhibits calcium and M current channels in rat sympathetic neurons via G proteins.

We characterized inhibition of N-type Ca2+ and M current K+ channels in rat superior cervical ganglion neurons by angiotensin II (angioII) using the patch clamp. Of 120 neurons, 97 showed inhibition of ICa (mean 32%), which was slow in onset and very slow to reverse under whole-cell recording conditions. This inhibition was blocked by the AT1 receptor antagonist losartan, attenuated by inclusion of 2 mM GDP-beta-S in the pipette, mostly pertussis toxin insensitive, half-sensitive to N-ethylmaleimide, and wholly voltage independent. With 20 mM instead of 0.1 mM BAPTA in the pipette, the inhibition was strongly attenuated; however, we detected no angioII-induced [Ca2+]i signal using the fluorescent indicator indo-1. IBa from cell-attached patches was reduced by bath-applied angioII (mean 33%), suggesting use of a diffusible cytoplasmic messenger. M currents were inhibited by angioII in 8 of 11 neurons (mean 50%) cultured overnight. Hence, a second agonist, angioII, may share the slow, second messenger-utilizing, pertussis toxin-insensitive signaling pathway used by muscarinic agonists.

Angiotensin II↗

PubMed1994

Effects of external Rb+ on inward rectifier K+ channels of bovine pulmonary artery endothelial cells.

Inward rectifier (IR) K+ channels of bovine pulmonary artery endothelial cells were studied using the whole-cell, cell-attached, and outside-out patch-clamp configurations. The effects of Rb+ on the voltage dependence and kinetics of IR gating were explored, with [Rb+]o + [K+]o = 160 mM. Partial substitution of Rb+ for K+ resulted in voltage-dependent reduction of inward currents, consistent with Rb+ being a weakly permeant blocker of the IR. In cells studied with a K(+)-free pipette solution, external Rb+ reduced inward IR currents to a similar extent at large negative potentials but block at more positive potentials was enhanced. In outside-out patches, the single-channel i-V relationship was approximately linear in symmetrical K+, but rectified strongly outwardly in high [Rb+]o due to a reduced conductance for inward current. The permeability of Rb+ based on reversal potential, Vrev, was 0.45 that of K+, whereas the Rb+ conductance was much lower, 0.034 that of K+, measured at Vrev-80 mV. The steady state voltage-dependence of IR gating was determined in Rb(+)-containing solutions by applying variable prepulses, followed by a test pulse to a potential at which outward current deactivation was observed. As [Rb+]o was increased, the half-activation potential, V1/2, changed less than Vrev. In high [K+]o solutions V1/2 was Vrev-6 mV, while in high [Rb+]o V1/2 was Vrev + 7 mV. This behavior contrasts with the classical parallel shift of V1/2 with Vrev in K+ solutions. Steady state IR gating was less steeply voltage-dependent in high [Rb+]o than in K+ solutions, with Boltzmann slope factors of 6.4 and 4.4 mV, respectively. Rb+ decreased (slowed) both activation and deactivation rate constants defined at V1/2, and decreased the steepness of the voltage dependence of the activation rate constant by 42%. Deactivation of IR channels in outside-out patches was also slowed by Rb+. In summary, Rb+ can replace K+ in setting the voltage-dependence of IR gating, but in doing so alters the kinetics.

Animals↗

PubMed1994

Ipsilateral hip and knee dislocation.

Hip and knee dislocations individually are two of the relatively limited orthopaedic emergencies. Long-term results of treatment of these two types of injury are associated with avascular necrosis of the femoral head, knee instability, and knee stiffness. Correct early diagnosis, including arteriography in the case of knee dislocation, is crucial. Prompt treatment consisting of closed or open reduction of the dislocations is necessary. Additional treatment involving knee ligament reconstruction is warranted to maximize knee function in healthy, active patients. Simultaneous occurrence of ipsilateral hip and knee dislocations is a particularly morbid injury. We report such a case to emphasize that early, aggressive treatment and extensive physical therapy can result in a functional and painless lower extremity.

Adult↗

PubMed1994

Improvement of sleep apnoea due to acromegaly during short-term treatment with octreotide.

Two acromegalic patients suffering from severe obstructive sleep apnoea syndrome were treated with the long-acting somatostatin analogue octreotide. Daytime sleepiness and fatigue improved within a few days. Repeat sleep studies performed after octreotide treatment revealed more confluent sleep with a shorter duration of sleep apnoea. Nocturnal hypoxaemia improved in one patient. Octreotide might be an effective noninvasive treatment for sleep apnoea of acromegaly.

Acromegaly↗

PubMed1994

Labrocapsular ligamentous complex of the shoulder: normal anatomy, anatomic variation, and pitfalls of MR imaging and MR arthrography.

Magnetic resonance (MR) imaging is a useful modality for evaluating the labrocapsular ligamentous complex (LCLC) of the shoulder. MR arthrography is an important and occasionally indispensable supplementary modality for accurate differentiation between normal and deranged glenohumeral joints. Because of the joint distention that occurs during MR arthrography, it is especially helpful in detecting subtle capsular derangement, as occurs in patients with atraumatic instability. Also, some of the pitfalls associated with MR imaging of the LCLC are less likely to occur with MR arthrography. Radiologists should look for several key abnormalities when evaluating MR images of the shoulder: an anterior or posterior Bankart lesion; a Hill-Sachs defect; a tear of the rotator cuff, glenoid labrum, or superior labrum-biceps tendon attachment; and loose bodies. Knowledge of normal anatomy, normal variations, and pitfalls in image interpretation related to evaluation of the LCLC will help the radiologist accurately detect debilitating derangements associated with glenohumeral instability.

Humans↗

PubMed1994

Modulation of Ca2+ channels by PTX-sensitive G-proteins is blocked by N-ethylmaleimide in rat sympathetic neurons.

The actions of N-ethylmaleimide (NEM), a sulfhydryl alkylating agent, on G-protein-mediated inhibition of N-type Ca2+ channels in adult rat superior cervical ganglion (SCG) neurons were studied using whole-cell voltage clamp. In SCG neurons, inhibition of ICa occurs by at least three separable pathways: one pertussis toxin (PTX) sensitive and voltage dependent, and two PTX insensitive and voltage independent. NEM blocked PTX-sensitive inhibition nearly completely, with only small effects on PTX-insensitive inhibition. Somatostatin inhibition is completely PTX sensitive and was wholly blocked by a 120 sec exposure to 50 microM NEM, with shorter exposure times producing a less complete block. Inhibition of ICa by norepinephrine (NE) is approximately half PTX sensitive and was also approximately half NEM sensitive. One component of muscarinic inhibition is PTX insensitive, voltage independent, and mediated by a diffusible cytoplasmic messenger; this pathway was largely spared by NEM treatment. Another pathway is also PTX insensitive and voltage independent, used by substance P, and was also largely NEM insensitive. Hence, in SCG neurons, NEM selectively inactivates PTX-sensitive G-proteins. We also find evidence that the PTX-insensitive action of NE is distinct from the other PTX-insensitive pathways, and therefore assign it to a fourth signaling pathway.

Animals↗

PubMed1993

Substance P and somatostatin inhibit calcium channels in rat sympathetic neurons via different G protein pathways.

We studied inhibition of N-type Ca2+ channels in rat superior cervical ganglion neurons by substance P (SP) and somatostatin-14 (Som). In whole-cell clamp, 70 of 82 acutely dissociated neurons showed inhibition (mean 37%) by 500 nM SP, and 54 of 61 showed inhibition by 240 nM Som (mean 57%). Pertussis toxin (PTX) blocked Som but not SP inhibition; intracellular dialysis with 2 mM GDP-beta-S attenuated inhibition with either peptide. Inhibition was voltage dependent with Som but not with SP. Neurokinin A (1 microM) or B was without effect, implicating NK1 tachykinin receptors. In cell-attached patches with bath-applied drugs, to test for a diffusible messenger, inhibition by SP or Som was only 8%. Thus, SP signaling is voltage independent and PTX insensitive; Som inhibition is voltage dependent and PTX sensitive; and both are membrane delimited.

Animals↗

PubMed1993

Direct in vitro measurement of forces in the cruciate ligaments. Part I: The effect of multiplane loading in the intact knee.

Specially designed load-transducers that measured the resultant forces exerted by the posterior and anterior cruciate ligaments on their respective femoral and tibial insertions were applied to eighteen fresh-frozen cadaveric knees for a series of controlled loading experiments. The mean force in the posterior cruciate ligament at 5 degrees of forced hyperextension of the knee was 23 per cent of the mean force in the anterior cruciate ligament. When the knee was hyperflexed by application of 10.0 newton-meters of bending moment to the tibia, the mean force in the posterior cruciate ligament was 55 per cent of that in the anterior cruciate ligament. Quadriceps tendon pull increased the force in the posterior cruciate ligament in twelve of the fourteen specimens to which it had been applied, at 80 and 90 degrees of flexion only. The force generated in the posterior cruciate ligament by applied internal tibial torque was greatest when the knee was in 90 degrees of flexion; the force in the anterior cruciate ligament was greatest when the knee was fully extended. External tibial torque generated force in the posterior cruciate ligament in only eight specimens, and only at 80 and 90 degrees of flexion. The levels of force that were generated in the posterior cruciate ligament by applied varus and valgus bending moment were greatest at 90 degrees of flexion of the knee; the levels of force in the anterior cruciate ligament were greatest with the knee in full extension. With the knee flexed 90 degrees and the tibia in neutral rotation, fifty newtons of applied posterior tibial force increased the mean force in the posterior cruciate ligament by 58.4 newtons; at full extension, no increase in the force in the ligament was recorded, indicating that tensed capsular structures were absorbing the applied load. When the tibia was internally or externally rotated by applied tibial torque, the increases in the force in the ligament from applied posterior tibial force were sharply diminished.

Aged↗