Free forearm flap for closure of difficult oronasal fistulas in cleft palate patients. There were four patients with palatal clefts who had been operated on many times previously but who still had large oronasal defects due to wound disruption. Moreover, there was considerable scar in the residual palatal tissue, which was contracted in the anteroposterior dimension. These patients were treated with a radial forearm flap transfer. The technical aspects of this reconstruction are emphasized, especially methods to enhance primary healing and to facilitate in setting the flap. Three of the patients were successfully reconstructed with one operation. The fourth had a small area of dehiscence anteriorly that was later closed with advancement of the flap tissue. There were no other complications. With the replacement of healthy tissue, the palate could be pushed further back to achieve better repair of the muscle. This would contribute to better speech function. In every patient, nasal regurgitation was eliminated, and speech quality improved significantly. The radial forearm flap is ideal for intraoral use, providing thin, hairless skin with a long, large-caliber vascular pedicle. It can reconstruct defects in one stage with well-vascularized tissue and minimal dissection of the palate. In a select group of cleft palate patients, this free-tissue transfer should be considered to achieve closure of large oronasal fistulas in patients with dense scar.


The radial forearm flap: a biomechanical study of donor-site morbidity utilizing sheep tibia. The use of vascularized bone grafts to reconstruct extremity and mandibular defects is now commonplace in reconstructive surgery. Fibula, scapula, iliac crest, rib, and metatarsal as well as the radial forearm osseocutaneous flaps have all been utilized for this purpose. Troublesome spiral fractures of the distal radius are the most common fractures associated with the use of the distal radius as a vascularized bone-graft donor site. This study was proposed to investigate the effect of donor-site bone loss on the strength of the radius under torsional (rotational) loading. Previous clinical series and experimental studies have not examined this aspect of distal radius loading after harvesting the bone graft. Fifty pairs of sheep tibiae were utilized in the experiment. Five pairs were used in a pilot study and 45 pairs were used in the main experiment. Five pairs of human radii were used for the control in the pilot study. The pilot study attempted to make a comparison between the human radius and the sheep tibia for experimental purposes. For the biomechanical study of donor-site defects, four study groups were examined with random assignment and matched pairs. The control group (group 1) had no alteration to the bone. Each test condition included five matched pairs of sheep tibiae. Experiment 1 compared the difference in the depth of the osteotomy defect. In doing this, one-third of the total length of the bone was removed in each of the following specimens to include (1a) 30 percent of the cross-sectional area of the total bone, (1b) 37 percent of the cross-sectional area of the total bone, and (1c) 50 percent of the cross-sectional area of the total bone. In experiment 2, the osteotomy shape was varied. Instead of the ends of the cuts being squared, the ends were beveled or rounded. Experiment 3 compared different lengths of bone removed in the osteotomy defect and included the following: In experiment 3a the diameter of the sheep tibia was measured at the incisura fibularis. This dimension was one diameter of bone, and a one-diameter length of bone was removed. In experiment 3b, a two-diameter length of bone was removed. In experiment 3c, a three-diameter length of bone was removed. In experiment 3d, a four-diameter length of bone was removed.(ABSTRACT TRUNCATED AT 400 WORDS)


Long-term results following velopharyngoplasty with a cranially based pharyngeal flap. Between 1980 and 1989, 82 velopharyngoplasties have been carried out in the Department of Oral and Maxillofacial Surgery at the Medical University of Hannover. Speech results of 51 of these patients, including 39 patients with cleft lip and palate, could be followed up in the context of a clinical follow-up examination. Besides evaluation of speech results by two senior speech pathologists and two untrained listeners, a frequency analysis of the speech results with a sonograph was obtained. Nasal air loss was documented with a fogged-mirror test and computer aerometry. Whereas in 37 of 51 patients a normal or almost normal colloquial speech could be demonstrated, 30 of 39 patients with cleft lip and palate showed a normal or almost normal realization of the test sentences. Thirty of the 37 patients (81.08 percent) with normal or almost normal colloquial speech showed extensive mobility of the lateral pharyngeal wall. Symmetry of the velopharyngeal flaps seemed to have no influence on the speech result. With a fogged-mirror test, an average reduction of mirror fogging from 2.0 rings preoperatively to 0.9 rings postoperatively could be shown. In 31 patients, there was no longer any air loss postoperatively. Besides one rupture of a flap, two flaps had to be diminished in their lateral dimensions because of excessive size. We regard the cranially pedicled pharyngeal flap as an important operative procedure for improving speech results, especially in cleft lip and palate patients.


An analysis of Le Fort I maxillary advancement in cleft lip and palate patients. We present a series of 24 consecutive cleft lip and palate patients aged 16 to 46 years (mean age 27 years) who underwent Le Fort I maxillary advancement by the senior author over the past 8 years. Two groups, one of 12 patients with wire fixation and one of 12 patients with miniplate fixation, were evaluated. Each group had 10 unilateral and 2 bilateral clefts. All patients were grafted with autogenous bone (8 cranial, 14 iliac, and 2 mandibular). Horizontal advancement was 3 mm to 2 cm (with a mean of 7.8 mm). Vertical movement ranged from a shortening of 5 mm to a lengthening of 1.3 cm (mean 2.3 mm of lengthening). The amount and timing of relapse were compared in both the horizontal and vertical dimensions. The plated group was more stable in both the horizontal and vertical dimensions (p < 0.05). No significant skeletal relapses occurred after the first year. Statistically significant dental relapse occurred only in the wired group. Three patients developed transverse collapse of the small maxillary cleft segment, and four developed incisor angulation to compensate for maxillary skeletal relapse. The presence of a pharyngeal flap at the time of advancement appeared to increase relapse in both horizontal and vertical dimensions (p < 0.03), but there were too few patients (7 of 24) with pharyngeal flaps to prove this conclusively. We also concluded that pterygomandibular grafting is not necessary to achieve excellent results using miniplate fixation; autogenous grafting of the anterior maxillary osteotomy alone provides the necessary stability.


The osteocutaneous free fibula flap: is the skin paddle reliable? This clinical and anatomic study was undertaken to see if the skin paddle of the osteocutaneous fibula flap could be made more reliable. Eighty cadaver limbs were dissected to evaluate the type, number, and location of the cutaneous perforators supplying the lateral leg. Three types of perforators were identified: septocutaneous, musculocutaneous, and a type we termed septomuscular, which does not actually run within the muscle substance but is adherent to the muscle. Although not a true musculocutaneous perforator, it should be treated as such clinically. Musculocutaneous perforators were found to be more numerous and more proximal than the septocutaneous perforators. Eighteen clinical cases demonstrate a 33 percent skin paddle survival when dissected as a septocutaneous flap and a 93 percent skin paddle survival when dissected as a septomusculocutaneous flap. In using the osteocutaneous fibula flap, it is recommended that a cuff of soleus and flexor hallucis longus be incorporated into the flap to help ensure flap viability.


Skin expansion in head and neck reconstructive surgery. We used a tissue-expansion technique to achieve soft-tissue reconstruction in congenital and acquired defects of head and neck. One hundred and fifty-five head and neck reconstructions have been performed, with a 6 percent rate of major complications. We present our planning and surgical approach for single areas. From a technical point of view, the only major difference from the rest of literature is the approach to the problem of periprosthetic capsule. In fact, we believe that complete removal of the capsule, which can be achieved without vascular risk thanks to a special technique, is necessary to obtain the best results.


Continuous versus intraoperative expansion in the pig model. Continuous tissue expansion utilizing a continuous infusion device that maintains a constant expander pressure was previously demonstrated to be feasible and successful in obtaining rapid tissue expansion in a canine model. Intraoperative tissue expansion has been described and has gained some clinical acceptance as a method to gain rapid expansion. We compared the efficacy of continuous tissue expansion versus intraoperative tissue expansion in a piglet model. After completing a pilot study, continuous tissue expansion was performed in six pigs (14.5 to 20 kg) on one flank over a 3-day period utilizing an improved prototype device; at the termination of continuous tissue expansion, intraoperative tissue expansion was performed on the opposite flank. There were no complications or continuous tissue expansion device malfunctions. Intraoperative tissue expansion gave a true gain in area of 7.4 percent, while continuous tissue expansion produced a 22 percent gain (p < 0.02). When the effects of both recruitment and expansion were added, continuous tissue expansion gave a dividend of 286 percent versus 192 percent for intraoperative tissue expansion (p < 0.01). Biomechanically, intraoperative tissue expansion skin showed few differences from unexpanded skin, while continuous tissue expansion skin showed a significant increase in stress relaxation (47.78 versus 38.74) and decrease in breaking strength. Histologic analysis revealed some epidermal hyperplasia and inflammation surrounding the continuous tissue expansion expander and some vascular congestion over the intraoperative tissue expansion expander. We conclude that continuous tissue expansion is superior to intraoperative tissue expansion and that the prototype device may be useful clinically.


Transcoronal blepharoplasty.

Transcoronal blepharoplasty. Some of the patients requesting blepharoplasty have a combination of excessive eyelid fat and brow ptosis but little or no dermatochalasis. Coronal brow lift, combined with transcoronal fat removal, serves these patients well. The prelevator fat pocket is easily entered from above by incising the periosteum of the anterior orbital roof just inside the orbital rim. Since the orbital septum and anterior lamella of the eyelid rim remain undisturbed, the result appears natural. Contraindications to the procedure include significant medical pocket fat and hair patterns that would exclude a coronal or hairline incision. Two complications, unilateral ptosis and unilateral chemosis, were temporary and totally reversible. Minor changes in the procedure have prevented the recurrence of these problems.


Correction of the pinched nasal tip with alar spreader grafts. A pinched nasal tip is caused by collapsed alar rims secondary to weak lateral crura. The resulting deformity can be corrected with alar spreader grafts--autogenous grafts of septal or auricular cartilage that are inserted between and deep to the remaining lateral crura to force them apart, propping up the caved-in segment. We describe the surgical technique, indications, and variations in design of alar spreader grafts and present representative results from our series of 38 patients.


Problem neck, hyoid bone, and submental myotomy. Despite significant attention to the cervical region over the last two decades, the hyoid bone has not received deserved recognition. In this report, the anatomy and role of the hyoid bone and suprahyoid muscles in cervicomental morphology are reviewed. From an analysis of cephaloxerograms on 54 patients, it was concluded that on a balanced neck, the most caudal border of the hyoid body is located at or above a line parallel to the Frankfort horizontal line passing through the most caudal border of the mandibular symphysis (menton). Of the muscles that control the position of the hyoid bone, the anterior belly of the diagastric, geniohyoid, and mylohyoid muscles pull the hyoid bone cephalad and anteriorly. The stylohyoid muscles, on the other hand, pull this bone cephalad and posteriorly, while the sternohyoid and omohyoid muscles pull it caudally. Transection of the first three muscles at their attachment to the posterior aspect of the mandible in patients with dysmorphic necks due to caudal and anterior hyoid position will allow posterior and cephalad relocation of this bone, which improves the neck contour. Sixteen patients, with an average follow-up of 27 months, have undergone this procedure, with cervicomental contour improvement in all cases. The degree of improvement ranged from 1 to 5 (5 being excellent): One patient was ranked 1, two patients were ranked 2, two patients were ranked 3, and the rest were ranked 4 or 5. One patient had overcorrection as a result of an aggressive concomitant submental lipectomy. Another patient had central depression in the submental area. None of the patients had difficulties with mandibular movement or swallowing.


Primary closure of human bite losses of the lip. Human bite injuries of the lip have, because of the potentially contaminated nature of the wounds, been managed by delayed repair after an interval of about 3 months or more when the infection was controlled and the wound healed. On the contrary, from 1985 to 1990, at a plastic surgery unit in Nigeria, a developing country, 37 patients with human bite losses of the lip were managed by an aggressive approach utilizing (1) a 5-day course of antibiotics locally known to be effective against bacterial flora and (2) immediate surgical operation employing the diamond wedge excision method under local anesthesia with direct wound closure. The results have been so favorable that this method of management of human bite injuries is considered a treatment advance.


Correction of type II breast deformities following conservative cancer surgery. Breast deformities following conservative cancer surgery are seen with increasing frequency and often represent difficult reconstructive problems. Type II deformities are characterized by localized tissue insufficiency, which can be due to skin insufficiency (type IIa), subcutaneous tissue insufficiency (type IIb), or both (type IIab). Correction of a locally damaged breast is a surgical challenge that can result in a fully restored breast if selection of the surgical procedure is properly carried out. A series of 37 patients who underwent correction of type II deformities from 1980 to 1989 was reviewed. Results obtained with different surgical procedures, including simple submuscular placement of traditional or expandable implants, breast reshaping, transposition of a latissimus dorsi muscle or musculocutaneous flap, TRAM flap, and reverse abdominoplasty, were evaluated. Aesthetic outcome was judged to be good or excellent in 78 percent of patients. Guidelines for selection of the most appropriate surgical procedure according to the defect's etiology, morphology, and location and to the breast's size and shape are presented.


Reconstruction of the radiated partial mastectomy defect with autogenous tissues. As conservative surgery and radiation therapy have become accepted treatments for early-stage breast cancer, increasing attention has focused on the cosmetic results of this technique. When partial mastectomy--a term which encompasses a diversity of excisional techniques--is followed by radiation therapy, breast defects characterized by parenchymal loss, nipple-areola complex distortion, and cutaneous abnormalities can occur. From 1981 to 1990, eight patients sought reconstructive correction of a radiated partial mastectomy deformity. Patients were from 42 to 70 years of age (mean 49 years). All had breast cancer, except for one patient with diffuse and chronic breast abscesses. Six patients were reconstructed with latissimus dorsi flaps and two with rectus flaps. No patient underwent reconstruction sooner than 1 year after completion of radiation therapy; for the entire group, a mean of 2.6 years elapsed from completion of radiation therapy to flap reconstruction of the breast. Mammograms were obtained on all the breast cancer patients before and after the myocutaneous flap procedure. Follow-up extended from 1 to 9 years after reconstruction (mean 3.6 years) and included both physical examination and serial mammographic evaluations. Myocutaneous flap reconstruction with either latissimus or rectus flaps achieved an aesthetic improvement of the partial mastectomy deformity in all eight patients. Complications consisted only of seroma formation in two patients following latissimus flap reconstruction. Mammographic evaluation revealed fibrofatty degeneration of the soft tissues of both types of flaps, a change that occurs as early as 6 months after operation and appears as a radiolucent area. The feasibility of mammography as a screening adjunct for recurrent cancer in this group of patients is demonstrated. Advantages of this technique of autogenous tissue reconstruction are improvement of contour deformities associated with conservative surgery and radiation therapy, preservation of normal, sensate breast skin, enhancement of symmetry with the contralateral breast, and avoidance of a prosthesis.


Unpredictable growth pattern of costochondral graft. Costochondral grafts have gained increasing popularity in reconstruction of the temporomandibular joint and condyle in children. This is a report on the long-term follow-up of eight adolescent patients who underwent reconstruction of the temporomandibular joint and ramus for correction of hemifacial microsomia or trauma-related temporomandibular joint ankylosis during varying periods of growth. Six patients had hemifacial microsomia, and two suffered from posttraumatic temporomandibular joint ankylosis. Average follow-up was 80.4 months. Four patients had excessive growth of the graft, one patient had suboptimal growth, and three patients had no growth. In addition, one patient had undergone four procedures for significant graft overgrowth. Based on this study and review of the literature, we have concluded that the growth pattern of the costochondral graft is extremely unpredictable, ankylosis is a common problem following a temporomandibular joint reconstruction with costochondral graft, and mandibular overgrowth on the grafted site can actually be more troublesome than the lack of growth. Furthermore, maxillary growth is proportionately influenced by vertical mandibular growth of the graft, while the horizontal maxillary growth is not altered. Ankylosis is a result of ossification of the cartilaginous portion and the three-dimensional graft overgrowth, aggressively extending beyond the cartilage graft boundary. Based on this study, we recommend that this procedure be performed only on severe deficiencies. Adequate amounts of soft tissue should be retained between the skull base and the graft, and we further recommend harvesting the graft from the fourth or fifth rib, which may reduce the potential for overgrowth.(ABSTRACT TRUNCATED AT 250 WORDS)


Protective effects of coenzyme Q10 on ischemia-induced reperfusion injury in ischemic limb models. We examined simple cold preservation of rat limbs in Euro-Collins' solution to elucidate the protective effect of coenzyme Q10 (CoQ10) on the ischemia-induced reperfusion injury in an ischemic extremity replant model. A total of 126 Lewis rat limb replants were performed. Limbs were amputated from donor rats and preserved at 4 degrees C in Euro-Collins' solution and were orthotopically grafted to isogeneic rats by microsurgical technique. In the experimental groups (n = 42), coenzyme Q10 (10 mg/kg) was injected intraperitoneally into the recipients about 1 hour before reperfusion. In the control groups (n = 84), the same dose of solvent was given by the same route. We evaluated vascular patency of anastomoses by direct observation or microangiogram and performed histologic examinations 7 days after replantation. In the control groups, the ischemic limit was 96 hours. Ischemic limbs treated with coenzyme Q10 showed a statistically significant (p < 0.05) improvement in vascular patency after 72 and 96 hours of ischemia. Histologically, bone viability with osteoblastic activity was maintained in coenzyme Q10-treated animals of the 72-hour ischemic group. We conclude that the protective effect of coenzyme Q10 on reperfusion injury is suggested in this replant model.


Clinicopathologic studies on human epithelial autografts and allografts. We compared the survival of cultured epithelial allografts and epithelial autografts applied to donor sites for split-thickness skin grafts. Before grafting, cultured epithelium was devoid of Langerhans cells (LCs) or lymphoid cells by immunohistochemical and electron microscopic examinations. The autografts attached to the wounds permanently, without any clinical evidence of rejection. In contrast, allografts, which were mismatched for MHC and blood-type antigens, appeared to adhere firmly only until day 7. By the second week, signs of graft rejection were apparent: The graft changed color, and the underlying dermis underwent "microerosion" and denudation. By the third week, the area formerly occupied by the allograft had the same coloration as ungrafted wounds and apparently had undergone reepithelialization by the host. Immunohistochemical and ultrastructural studies clearly demonstrated that host Langerhans-like cells (without Birbeck granules) appeared in both autografts and allografts. However, these cells were numerous and distributed widely throughout allografts, whereas they were scarce and confined to the basal layer of autografts. Typical Langerhans cells (containing Birbeck granules) were present in the prickle-cell layer of autografts by day 7. The present study strongly indicates that allografts of cultured epithelium are rejected. Furthermore, given the known ability of Langerhans-like cells to function as accessory cells in T-cell activation, our results point to a role for host Langerhans-like cells in immunologically mediated rejection of the epithelial allografts.


Controlling intraoperative and postoperative nasal bleeding. An indwelling nasal suction tampon is described that effectively controls both intraoperative and postoperative nasal hemorrhage. The significant benefits of this device are better intraoperative control for the surgeon and less complicated postoperative recovery. I do not have any financial involvement in this device, but I would like other nasal surgeons to benefit from its particular advantages. The device is available under the trade name Instant and may be obtained from Innovations by Westmed, 3351 E. Hemisphere Loop, Tucson, Ariz. 85706; (602) 294-7987.


Epidemiology of cancer in the United States. Malignant neoplasms are responsible for more than half a million deaths annually and 22.5% of all deaths in the United States. Cancer is the second leading cause of death overall and the leading cause of death among Americans aged 35-64. Within the next decade it may become the leading cause of death. Cancers of digestive and respiratory organs are responsible for 53% of all cancer deaths. Certain subgroups are at elevated risk for various cancers. For example, sun-sensitive or excessively sun-exposed young white adults, young black women, and elderly patients are at increased risk for cutaneous melanoma, breast cancer, and colon cancer, respectively. Black men have the greatest risk for both lung cancer and cancer of the prostate. Acute lymphoblastic leukemia and solid tumors of the brain and nervous system are the most frequent forms of malignancy occurring among children less than or equal to 14 years. Office screening is the traditional method for identifying cancer victims as early as possible. A suitable screening test should be rapid, simple, inexpensive, and impose minimal discomfort. There must be a window of opportunity available to identify the cancer during a detectable preclinical phase, and therapeutic modalities must be available to alter progression. An office screening test for cancer may have any one of four outcomes, and three of them are bad. False negatives are the worst adverse outcome because cancer remains undetected despite screening. An epidemic of lung cancer, caused by cigarette smoking, is occurring in all race and sex groups. If Americans stopped smoking, 87% of lung cancer deaths could be prevented. Tobacco abuse also is a major risk factor for cancer of the esophagus, larynx, and oral cavity. Cigarette smoking is a contributing factor for cancer of the bladder, kidney, and pancreas, and it has been associated with both cervical cancer and cancer of the stomach. Smoking and smokeless tobacco cessation endorsements, messages, and programs must be part of routine disease prevention and health promotion activities in every primary care practice. More than 1 million Americans became new cancer victims last year, and more than 1 million additional cases will be detected this year. Because of the striking variability in state and regional patterns of various forms of cancer, geographic location of a practice may influence the frequency of cancers seen. Four sites (breast, prostate, lung, colon, and rectum) were responsible for 55% of cancer mortality and 56% of all new cases of cancer detected during 1991.(ABSTRACT TRUNCATED AT 400 WORDS)


Cancer in socioeconomically disadvantaged populations. This article presents a summary of the health status of the disadvantaged populations in the United States, with specific regard to the incidence, treatment, and mortality of cancer. It begins with an historical overview of health care for the poor in this country, and continues with an explanation of the risk factors prevalent, if not inherent, in the life-style associated with low socioeconomic status, such as poor diet, cigarette smoking, and ignorance of preventive health measures and screening techniques. It includes a discussion of the different types that are overrepresented in this population and of the barriers to preventive care and treatment that still exist. The most important of these is decreased access to continuous medical care because of a lack of health insurance and an overdependence on emergency room treatment for all health care. The final section reviews solutions that have been preferred by physicians, nurses, lawmakers, public health workers, and community advocates for the poor. The most important parts of the solution are patient education for preventive health care, disease warning signs, and screening techniques and an overhaul of the present system of providing health care to ensure equal access and treatment for all members of the society.


Geriatric oncology.

Geriatric oncology. The incidence and prevalence of cancer will continue to rise in the elderly. Malignancies can present differently and have altered courses in the elderly. Heterogeneity exists within the geriatric population, and chronologic age alone should not be used to exclude older cancer patients from consideration for standard diagnostic therapeutic approaches. Early detection of malignancies in the aged remains a problem, and geriatric screening issues are discussed.


Risk factors for cancer.

Risk factors for cancer. It is no longer reasonable to divide cancers into those that are genetic in origin and those that are environmental in origin. With rare exception, carcinogenesis involves environmental factors that directly or indirectly exert a change in the cell's genome. Virtually all causes of cancer are multifactorial, sometimes involving an inherited predisposition to the carcinogenic effects of environmental factors, which include chemicals, ionizing radiation, and oncogenic virus. Carcinogenesis is a multistep process including induction, promotion, and progression. Initiation requires an irreversible change in the cellular genome, whereas promotion is commonly associated with prolonged and reversible exposure. Tumor progression results in genotypic and phenotypic changes associated with tumor growth, invasion, and metastasis. Most information on human cancer risk is based on epidemiologic studies involving both exposed and unexposed individuals. The quality of such studies depends on their ability to assess the strength of any association of exposure and disease and careful attention to any potential bias. Few cancers are inherited in a Mendelian fashion. Several preneoplastic conditions, however, are clearly inherited and several malignancies demonstrate weak familial patterns. Environmental factors may exert their effect on DNA in a random fashion, but certain consistent changes, including specific translocations of genetic information, are often found. Currently, there is great interest in the close proximity of certain oncogenes governing growth control to the consistent chromosomal changes observed. Such changes may represent a final common pathway of action for environmental carcinogens. Sufficient laboratory and epidemiologic evidence exists to establish a causal association of several chemical agents with cancer. The most important carcinogenic chemicals are associated with life-style factors, whereas agents related to other environmental, occupational, or medical exposure are numerically less important. Most chemical agents exert their carcinogenic effects as electrophilic reactants covalently binding to DNA. Certain agents such as asbestos are carcinogenic by virtue of their physical properties. Several short-term tests have been used to screen for chemical carcinogens. Whole-animal studies remain the standard for predicting carcinogen risk in humans, although major limitations in such studies exist. Ionizing radiation also exerts its carcinogenic effect through damage to cellular macromolecules including DNA. Excess cancer risk appears after a latent period of several years following exposure. Risk increases in approximately a linear fashion in proportion to the radiation energy, cumulative dose, and a variety of host biologic factors. The greatest source of average radiation exposure to the US population is from the uranium decay product radon.(ABSTRACT TRUNCATED AT 400 WORDS)


Smoking cessation in office practice.

Smoking cessation in office practice. There can be no question that smoking is a modern version of plague; that, as Camus points out, the public does not comprehend its true nature. As in the metaphorical community in Camus' narrative, the struggle of individuals against the pestilence (including official obstruction) is imperative. Physicians have multiple opportunities to join the war against tobacco. This article has shown how one may help individual patients in smoking cessation or interruption of its initiation and has suggested other activities by which physicians can become health promotion specialists. By assisting in the process by which smoking loses its appeal, educating community leaders and medical organizations, and becoming exemplars of prohealth activity, we can make a difference in the health of our communities and our patients.


Principles of cancer screening for clinicians. This chapter has outlined some principles of tumor growth, test characteristics, and the evaluation of screening technologies. We have emphasized that test specificity is the critical parameter in the evaluation of technologies because it is the healthy people who will suffer the most from the adverse effects of screening. We have also emphasized that the efficacy of a test is best evaluated by examining mortality reductions in comparable populations. The purpose has been to assist clinicians with their interpretation of the literature. Busy clinicians may not always have the time or inclination to do this themselves. In those cases they need to examine how organizations who make recommendations are coming to their conclusions because it is physicians, not organizations that will do the screening. In particular, it is important to ask the following: (1) Were criteria followed to justify the recommendations being made? (2) If so, what were they, and can the organization demonstrate that they are being met? (3) What perspectives and biases do the organizations bring to the judgments they inevitably have to make? (4) Do you share those perspectives? and (5) When the recommendation is adopted, can you guarantee that it will "first do no harm."


Barriers and incentives of physicians and patients to cancer screening. It is imperative that the health care system provide mechanisms to improve cancer control. The most effective way of limiting cancer morbidity and mortality is by prevention (modification of behaviors that increase cancer risk), and by early diagnosis in the asymptomatic stage of the disease, which allows for curative therapies. This article has enumerated barriers that make preventive and early diagnostic maneuvers more difficult for both patients and physicians. Some of the barriers are common to both patients and physicians, such as discontinuity of care. The barriers were discussed from both perspectives. Suggestions were made for modification of these barriers, so that incentives might make provision of the preventive and early diagnosis more likely. The incentives are attainable; however, to make improvements on a large scale will require the efforts of the public, physicians, and the health care system. It will effect physicians from the beginning of their medical education and through their entire practice. A large amount of effort directed at a focused population by a small team of health care workers can make a large difference in preventive care. This was shown effectively by a general practitioner in England who undertook a 15-month "campaign" on a "deprived" community, and raised the level of preventive care to that of an "endowed" community. This type of effort by an individual is desirable, but much smaller individual efforts directed over an entire population can have a much greater ultimate effect. That is why the efforts must be directed toward the primary care physician. These physicians care for the majority of the population, so if each primary care doctor increased current efforts of prevention by just three patients per day, then over the entire population inestimable improvements on preventive care would result. There is some evidence that improvements in preventive care are occurring. As further research is directed at how best to provide preventive services in the physician's office, our skills and effectiveness will improve. Each physician should accept as his or her responsibility the ongoing preventive needs of the population he or she serves. The prevention and early diagnosis of cancer can be coordinated in the office with episodic care to minimize costs. The necessary knowledge and technology are available, application is the key. By applying these in a cost-effective way, we can hopefully attain control of cancer in the next decade.


Skin cancer prevention and screening.

Skin cancer prevention and screening. Prevention and early detection of skin cancers are crucial to reducing morbidity and mortality. Armed with the above information and with some experience, the primary care physician can understand risk factors and recognize common benign and malignant skin tumors. This allows the primary care physician to play a key role in teaching patients about skin cancer prevention and in screening patients for skin cancers.


Breast cancer screening.

Breast cancer screening. Breast cancer, as the second leading form of cancer death among women, causes significant morbidity and mortality. The primary care physician can help raise the survival rate of women with breast cancer by providing important screening procedures that will lead to early diagnosis and treatment. Screening mammography and regular breast physical examinations are the current screening procedures of choice. Although there is still considerable debate over the age and interval at which women should undergo screening (see Table 1 for recommendations from various organizations), the primary care physician's recommendation is the single most important factor and will certainly lead to a higher screening rate for women in the greater at-risk age groups. Judicious use of these screening procedures should allow primary care physicians to catch more breast cancers at an early, curable stage.


Cervical cancer screening. Past success and future challenge. Population screening for cervical cancer resulted in significant reduction in the morbidity and mortality from cervical cancer. An increased understanding of the relationship of HPV infection with cervical cancer and the natural history of cervical cancer precursor lesions further solidifies and expands the biological basis for cervical cancer screening. Pap tests in asymptomatic women remain the cornerstone of cervical cancer screening. Clinicians should be cognizant of the significant false-negative rate of Pap smears. Meticulous attention to proper Pap smear technique is necessary to maximize the sensitivity of the test. Further research is needed to establish the role of cervicography and HPV DNA hybridization techniques in cervical cancer screening.


Screening for gynecologic cancer. Vulvar, vaginal, endometrial, and ovarian neoplasms. The success of the Pap smear in screening for cervical cancer illustrates many of the tenets of screening for disease. Unfortunately, no other gynecologic malignancy shares this success. Detection of most gynecologic malignancies occurs once they have become symptomatic and on clinical examination at the interval cancer-related checkup as recommended by the ACS. These examinations, done yearly in women older than 40 and every 3 years in younger women, can go a long way in the detection of genital tract disease. In detecting vulvar neoplasms, visual inspection of the entire perineum coupled with palpation to include Bartholin's glands and early biopsy of suspicious vulvar lesions promotes earlier diagnosis. Self-examination similar to breast self-examination and increased patient awareness are potential education goals for physicians as well as cancer and medical societies. Vaginal examination at the cancer checkup should continue. The finding that most vaginal cancers are picked up by abnormal cytology while they are still asymptomatic argues strongly for Pap testing after menopause. The knowledge that women who are status posthysterectomy for benign disease are not protected from developing vaginal cancers mandates continued Pap testing in this population as well. Because endometrial cancer is common, primary care physicians should maintain a high index of suspicion. Aspiration biopsy is a simple office-based procedure with low risk and good yield, and any woman in the perimenopausal and postmenopausal period who presents with atypical bleeding patterns should be evaluated. Although not recommended as a general screening test, the ACS does advocate endometrial sampling in the high risk woman at the time of menopause. The greatest challenge to primary care physicians may be the early detection of ovarian cancer. No single test is available, nor is any advocated in screening for this lethal disease. Currently, only periodic physical examination is recommended at the cancer checkup interval. Ultrasound, both transabdominal and transvaginal, may help in detecting adnexal masses, but is not sensitive enough to differentiate benign from malignant lesions. In this setting, and in the patient with suspected ovarian cancer, CA 125 and AFP may be helpful in determining which patients require surgical exploration. Women with positive family histories for ovarian cancer require greater vigilance and close follow-up with serial ultrasound and CA 125 determinations. As the population ages, cancer, which is primarily a disease of age, will continue to increase in incidence.(ABSTRACT TRUNCATED AT 400 WORDS)


Colorectal cancer screening.

Colorectal cancer screening. Colorectal cancer is a common and devastating disease. Many authorities recommend screening asymptomatic person, although the benefit of such screening is without scientific validation. Each of the screening modalities available has been examined, and their merits and shortcomings have been discussed. Surveys have indicated that primary care physicians generally agree with screening asymptomatic patients, but only a minority actually comply with the recommendations. Patient acceptance also varies. Thus, while specialty boards and panels of experts attempt to arrive at policies for the general population, primary care physicians must interact with the individual patient. Until data from ongoing prospective screening studies are available and cost-benefit issues are resolved, screening for colorectal cancer will remain at the discretion of physicians and their patients. There is insufficient evidence to support either continuing or discontinuing the recommended examinations for asymptomatic patients. The screening examinations can be recommended on the basis of a theoretical benefit, however. They can be performed with a minimum of risk of injury or side effects. Certain patients can be identified as being at above-average risk and deserving of more consideration. If aware of the benefits and limitations of colorectal cancer screening, primary care physicians can decide how to implement colorectal cancer screening in their clinical practice.


Plasma beta-endorphin and natural killer cell activity in major depression: a preliminary study. Low concentrations of beta-endorphin have been found to enhance human natural killer (NK) cell activity in vitro. Both beta-endorphin and NK activity are changed by clinical depression. To evaluate whether circulating concentrations of beta-endorphin have a role in the in vivo modulation of cellular immunity in humans, we measured plasma beta-endorphin and NK cell activity in 14 depressed patients and 14 age-matched control subjects. In the depressed patients, both plasma beta-endorphin and NK cell activity were reduced to 76% and 57%, respectively, of the mean levels in the control subjects. In addition, beta-endorphin showed a significant positive correlation with lytic units of NK cell activity in the combined group of all subjects and in the patient group (p = 0.04), but not in the control group. The study supports the hypothesis that circulating endorphin is correlated with NK cell activity in vivo. This correlation may be higher in the depressed patient group.


Hormone responses to fenfluramine and placebo challenge in endogenous depression. Plasma prolactin and cortisol levels after oral administration of d-l fenfluramine hydrochloride (60 mg) and placebo were examined in 24 endogenously depressed patients and 21 age- and sex-matched normal control subjects in a randomized, double-blind study. Prolactin levels were significantly increased by fenfluramine in both groups, but the response was significantly blunted in the depressed patients compared with the controls. This effect was partially dependent upon elevated baseline cortisol levels in the depressed group and was also influenced by a history of weight loss. Plasma cortisol levels were not increased by fenfluramine in either group. These findings confirm previous reports and suggest that patients with endogenous major depression are characterized by central serotonergic hyporesponsivity. The need to account for baseline effects on hormonal responses to putative serotonergic agents is supported by the findings; however, these effects appear to be less striking when endogenicity is a prominent clinical feature of the depressive syndrome. The apparently complex influence of weight loss on prolactin response to serotonergic challenge remains to be clarified as well as the role played by the bioavailability of the challenge drug and its metabolite.


Behavioral engagement level, variability, and diurnal rhythm as a function of bright light in bipolar II seasonal affective disorder: an exploratory study. Six patients with bipolar II seasonal affective disorder (SAD) and seven normal control subjects rated their moods in winter at six fixed times each week-day during 1 week of dim and 2 weeks of bright light. The scales rated represent the mood dimension specifically associated with depression, a dimension here called behavioral engagement (BE). Compared with controls, depressed SAD subjects (1) showed lower BE levels across all rating times of the day, (2) were more likely to show diurnal variation in BE, (3) displayed more between-day instability in BE diurnal rhythm, and (4) exhibited greater short-term lability (change within 3 hours) in BE. Bright light reduced or eliminated all group differences in BE level and variability.


Blood levels of melatonin, serotonin, cortisol, and prolactin in relation to the circadian rhythm of platelet serotonin uptake. Blood levels of melatonin, serotonin, cortisol, prolactin, and serotonin uptake by platelets were measured at 08:00, 14:00, 20:00, 02:00, and 08:00 hours in 10 healthy men who ranged in age from 27 to 35 years. The Km values of serotonin active transport by platelets were significantly correlated with melatonin blood levels. There were no other significant correlations. The secretion of steroid hormones and prolactin showed an increase at 02:00 hours; levels of prolactin decreased at 08:00 hours, but steroid levels continued to rise. This finding suggests either a direct effect of melatonin on serotonin active transport or the influence of the suprachiasmatic nucleus on serotonin uptake by platelets. It is also possible that there is a simultaneous decrease in serotonin uptake and decline from peak levels of melatonin due to the rise in steroid secretion.


Phototherapy with broad spectrum white fluorescent light: a comparative study. The principles of photobiology suggest that the antidepressant effect of phototherapy depends on the dose and spectrum of light. We investigated the effect of spectrum by comparing two broad spectrum fluorescent light sources with different spectral distributions. In a crossover design, 11 patients with seasonal affective disorder (SAD) were treated with broad spectrum fluorescent and cool white light for 7 days. Scores on the Hamilton Rating Scale for Depression were reduced from 22.5 to 8.1 with broad spectrum fluorescent light and from 23.5 to 8.8 with cool white light. The results suggest that both light sources are effective treatments.


Effect of chronic antidepressant treatment with adinazolam and desipramine on melatonin output. Output of melatonin or its main metabolite, 6-sulphatoxy melatonin, provides an index of noradrenergic activity in the pineal gland, which is of interest in major depression and during its treatment with antidepressants. Fifteen female depressed outpatients did not differ in levels of 24-hour urinary 6-sulphatoxy melatonin compared with 13 female control subjects. However, a subgroup of the depressed patients (n = 9) who were treated with desipramine showed a significant elevation of 6-sulphatoxy melatonin levels after 1 week of treatment and a return to baseline levels after 6 weeks. There was also a significant negative correlation between 6-sulphatoxy melatonin levels and symptom severity as measured by the Hamilton Rating Scale for Depression after 3 weeks of treatment with desipramine. The other subgroup of depressed patients (n = 6) were treated with adinazolam, a benzodiazepine with antidepressant properties. Despite comparable antidepressant effects to those achieved with desipramine, adinazolam was not associated with any apparent change in 6-sulphatoxy melatonin output during 6 weeks of treatment. There was also no correlation between 6-sulphatoxy melatonin levels and symptom severity.


Increased prevalence of the cavum septum pellucidum in magnetic resonance scans and post-mortem brains of schizophrenic patients. A cavum septum pellucidum (CSP) has been regarded as an incidental finding of little clinical importance. However, an association between this developmental anomaly and a diagnosis of psychosis has previously been reported. We determined the prevalence of the CSP in parallel studies of brain scans obtained with magnetic resonance (MR) imaging and in the post-mortem brains of schizophrenic patients compared with normal controls. We found a significantly increased prevalence of the CSP in both the MR scans and post-mortem brains of schizophrenic patients compared with controls. In the MR study, 17 of 81 (21%) schizophrenic patients but only 1 of 46 (2%) control subjects had a CSP. In the post-mortem study, 17 of 28 (61%) schizophrenic patients and 12 of 39 (31%) normal controls had a CSP. The increased prevalence of a CSP in schizophrenic patients further indicates that anomalous development of the limbic system is an important aspect of this disorder.


Quantitative magnetic resonance imaging in heroin- and cocaine-dependent men: a preliminary study. Quantitative magnetic resonance imaging (MRI) of the brain was performed in nine drug-dependent men with a primary diagnosis of opioid and/or cocaine dependence, and 10 age-matched, non-drug-dependent controls. Individuals were screened for the presence of gross cerebral abnormalities before T1 and T2 analyses. Regional T1 and T2 times were calculated on a single 5-mm thick axial slice positioned just below the caudal margin of the lateral ventricles, passing through the caudate and putamen. A voxel of interest (VOI) cursor was placed bilaterally within the putamen, caudate, frontal gray matter, frontal white matter, or posterior white matter. T1 and T2 values were determined for each VOI using an iterative chi 2 minimization program. T1 and T2 relaxation times did not differ significantly between the subject groups in any brain region studied. These results suggest that T1 and T2 relaxation times may not identify microstructural central nervous system changes resulting from chronic opiate and cocaine abuse.


Topographic quantitative EEG amplitude in recovered alcoholics. Topographic measures of electroencephalographic (EEG) amplitude were used to compare recovered alcoholics (n = 14) with sex- and age-matched control subjects. Delta, alpha, and beta activity did not distinguish the groups, but regional differences in theta distribution did. Recovered alcoholics showed more uniform distributions of theta amplitudes in bilateral anterior and posterior regions compared with controls. Because a minimum of 5 years had elapsed since the recovered alcoholic subjects fulfilled DSM-III-R criteria for alcohol abuse or dependence, it is unlikely these EEG theta differences reflect the effects of withdrawal.


Segmentation techniques for the classification of brain tissue using magnetic resonance imaging. A technique is described for classifying brain tissue into three components: gray matter, white matter, and cerebrospinal fluid. This technique uses simultaneously registered proton density and T2-weighted images. Samples of each of the three types of tissue are identified on both image sets and used as "training classes"; these tissue samples are then used to generate a linear discriminant function, which is used to classify the remaining pixels in the image data set. Effects of varying the location and number of training classes have been explored; six pairs of training classes have been found to yield a suitable classification. Interrater and test-retest reliability have been examined and found to be good. Intrascanner and interscanner reproducibility has also been evaluated; classification rates are reproducible within the same individual when the same scanner is used, but in this study poor reproducibility occurs when the same individual is scanned on two different scanners. The validity of the technique has been tested by examining correlations between traced and segmented regions of interest, evaluating correlations with age, and conducting phantom studies, in addition to using visual inspection of the classified images as an indication of face validity. From all four perspectives, the method has been found to have good validity. Additional applications, strengths, and limitations are discussed.


Brain lithium concentration by 7Li- and 1H-magnetic resonance spectroscopy in bipolar disorder. A method was developed to measure lithium concentrations in the human brain using in vivo 7Li- and 1H-magnetic resonance spectroscopy (MRS). Lithium concentrations measured by MRS in 10 lithium-treated bipolar patients were at the half level of those measured in serum. Serial measurements indicated that lithium concentrations in the brain increased markedly during manic episodes, while serum concentrations were unchanged. These findings suggest that in vivo measurements of lithium concentrations in the brain, combined with measurements of concentrations in serum, may be useful in monitoring the effects of therapeutic drugs.


Pagophagia, or compulsive ice consumption: a historical perspective. Pagophagia, or the excessive consumption of ice or iced drinks, is popularly regarded as a novel manifestation of pica, which has emerged, predominantly in the USA, over the last 30 years. However, a sampling of historical sources reveals that not only are there warnings in the writings of both Hippocrates and Aristotle concerning the dangers of excessive intake of cold or iced water, but a series of medical works, from the sixteenth century on, incorporate discussion and illustrative case histories about the detrimental effect of immoderate usage of cold water, ice and snow, frequently in the context of disordered eating.


Eye-tracking dysfunction in the affective psychoses and schizophrenia. Smooth pursuit eye movements to a sinusoidally moving target were recorded using the electro-oculogram in 49 subjects with bipolar disorder, 19 with major depressive disorder and 61 with definite schizophrenia, and compared with 145 normal controls. The signals were analysed in the frequency domain to yield a signal to noise ratio that is known to relate to accuracy of smooth pursuit. Smooth pursuit was found to be significantly poorer in schizophrenics than in bipolars, major depressed or controls. Eye-tracking performance was independent of the effects of neuroleptics, tricyclic antidepressants or lithium, and was not altered by the severity of depression in the affective psychoses. There was a small, but significant worsening of smooth pursuit with age in controls and schizophrenics, but this did not account for the group differences. The results support the view that among the major psychoses eye-tracking dysfunction is specific to schizophrenia.


Familial calcification of the basal ganglia: a case report and review of the literature. Although calcification of the basal ganglia is a relatively common and asymptomatic finding on cranial computed tomography, familial idiopathic calcification of the basal ganglia (ICBG) is a rare disorder with neurological and behavioral manifestations. Attention has recently been drawn to the frequency with which cases are diagnosed as schizophrenic (Cummings et al. 1983; Lowenthal, 1986; Davison, 1987). We report a family in which a mother and son have ICBG, but while the son has a paranoid schizophrenia and intellectual deterioration, the mother shows no psychiatric illness. A review of the relevant literature suggests that psychosis is not as common as usually supposed, and may only be coincidentally associated with familial ICBG. Moreover, we find little convincing evidence that familial ICBG is an independent entity; instead, and in agreement with earlier authorities (Bruyn et al. 1964), we argue that published accounts and our own cases provide evidence that the condition is related to pseudo-hypoparathyroidism (PHP) and, therefore, may be due to a defect in a guanine nucleotide binding protein.


The relationship between depression and anxiety: construction of a prototypical anxiety and depression scale. The question of the relationship between anxiety and depression remains to be solved. The fact that clinical pictures show substantial overlap makes it difficult, using conventional instruments, to distinguish between the co-occurrence of anxiety and depression and overlap in definitions and measurement of the two syndromes. This calls for the construction of scales which exclude symptoms common to both syndromes and incorporate symptoms specific only to anxiety or only to depression; i.e. scales with maximum discriminant validity. This article describes the construction of two such scales based on PSE symptoms; a prototypical anxiety scale and a prototypical depression scale. In a sample of 134 non-psychotic psychiatric out-patients these scales show good reliability and validity, both as a measure of severity and as a screening device. Compared to the Hamilton anxiety and depression scales (HARS and HRSD), the correlation between the prototypical anxiety and depression scales is low.


The anatomy of melancholia--focal abnormalities of cerebral blood flow in major depression. Using positron emission tomography (PET) and 15Oxygen, regional cerebral blood flow (rCBF) was measured in 33 patients with primary depression, 10 of whom had an associated severe cognitive impairment, and 23 age-matched controls. PET scans from these groups were analysed on a pixel-by-pixel basis and significant differences between the groups were identified on Statistical Parametric Maps (SPMs). In the depressed group as a whole rCBF was decreased in the left anterior cingulate and the left dorsolateral prefrontal cortex (P less than 0.05 Bonferroni-corrected for multiple comparisons). Comparing patients with and without depression-related cognitive impairment, in the impaired group there were significant decreases in rCBF in the left medial frontal gyrus and increased rCBF in the cerebellar vermis (P less than 0.05 Bonferroni-corrected). Therefore an anatomical dissociation has been described between the rCBF profiles associated with depressed mood and depression-related cognitive impairment. The pre-frontal and limbic areas identified in this study constitute a distributed anatomical network that may be functionally abnormal in major depressive disorder.


Bulimia nervosa and major depression: a study of common genetic and environmental factors. A genetic analysis of the co-occurrence of bulimia and major depression (MD) was performed on 1033 female twin pairs obtained from a population based register. Personal interviews were conducted and clinical diagnoses made according to DSM-III-R criteria. Additive genes, but not family environment, are found to play an important aetiological role in both bulimia and MD. The genetic liabilities of the two disorders are correlated 0.456. While unique environmental factors account for around half of the variation in liability to both bulimia and MD, these risk factors appear to be unrelated, i.e., each disorder has its own set of unique environmental risk factors. Thus, the genetic liability of bulimia and MD is neither highly specific nor entirely non-specific. There is some genetic correlation between the two disorders as well as some genetic and environmental risk factors unique to each disorder. Limitations and directions for future research are discussed.


Early onset bulimia nervosa: who is at risk? A retrospective case-control study. The aim of the study was to compare the clinical features and predisposing characteristics of patients with an early onset of bulimia nervosa with those with a more typical onset. Twenty-three cases of early onset bulimia nervosa (onset age 15 or below) were compared with 23 sex- and class-matched cases of typical onset (onset age 17 to 21) using a retrospective case-control design. No difference was found in eating symptomatology between the two groups. Deliberate self-harm was more frequent in the early onset group, and there was a trend towards more depression among their relatives. Inadequate parental control occurred more often in the early onset group, but other indicators of intrafamilial disturbance did not differ in the two groups. There was also a trend for the early onset group to be exposed to more cultural stress as a result of family migration. Early onset patients were found to have a higher loading on risk factors than typical onset patients.


The epidemiology of psychiatrist-ascertained depression and DSM-III depressive disorders. Results from the Eastern Baltimore Mental Health Survey Clinical Reappraisal. Psychiatrists used a semi-structured Standardized Psychiatric Examination method to examine 810 adults drawn from a probability sample of eastern Baltimore residents in 1981. Of the population, 5.9% was found to be significantly depressed. DSM-III major depression (MD) had a prevalence of 1.1% and 'non-major depression' (nMD), our collective term for the other depressive disorder categories in DSM-III, had a prevalence of 3.4%. The two types of depression differed by sex ratio, age-specific prevalence, symptom severity, symptom profiles, and family history of suicide. Analyses using a multiple logistic regression model discerned that both types of depression were influenced by adverse life events, and that nMD was influenced strongly by gender, marital status, and lack of employment outside the home. Neither type of depression was influenced by income, education, or race. This study validates the concept of major depression as a clinical entity. Future studies of the aetiology, mechanism, and treatment of depression should distinguish between these two types of depression.


Parental representations of melancholic and non-melancholic depressives: examining for specificity to depressive type and for evidence of additive effects. Several studies have suggested that 'anomalous parenting', as measured by the Parental Bonding Instrument (PBI), may be a differential risk factor to subsequent depression in adulthood--being irrelevant to melancholia but over-represented in non-melancholic depressive disorders. Such a 'specificity' effect is confirmed in our current sample of 65 melancholic and 84 non-melancholic depressed patients. Secondly, we examine the risk to depression effected by exposure to one parent with an anomalous parental style, and the extent to which that risk is modified by characteristics of the other parent. We find clear evidence of additive effects with the risk to non-melancholic depression being raised by exposure to 'anomalous parenting' from two parents. Of the varying parental styles measured by the PBI, low parental care from both parents provided the highest risk to non-melancholic depression (being 4-7 time higher in one sample and 13-27 times higher in the other).


Coping subtypes for men with coronary heart disease: relationship to well-being, stress and Type-A behaviour. We used cluster analysis to delineate coping subtypes in a sample of 166 men with coronary heart disease who completed the Antwerp out-patient rehabilitation programme. These subtypes were identified on the basis of three well-defined superordinate traits that were selected from a comprehensive taxonomy: negative affectivity, social inhibition, and self-deception. Using Ward's minimum variance method and the cubic clustering criterion, we identified four coping subtypes; low-negative affectivity (N = 48), high-negative affectivity (N = 30), inhibited (N = 62), and repressive (N = 26) individuals. The accuracy of the resulting classification was demonstrated across parallel data sets and was further validated against external, health-related correlates that were not included in the clustering. The identified coping subtypes were significantly related to self-reports of subjective distress/perceived stress, ratings of Type A behaviour and anger-in, return to work, prevalence of chest-pain complaints, and use of minor tranquillizers and sleeping pills. The major findings of this study suggest that (a) male coronary patients represent a heterogeneous population with distinctly different coping subtypes, and that (b) a relatively small number of homogeneous subtypes can account for a substantial amount of variance in subjective well-being, coronary-prone behaviour, and return to work. These findings indicate that psychosomatic research should focus on how superordinate traits interact within individuals and corroborate the appropriateness of a class model to describe coping styles of male coronary patients. It is argued that discrepant findings across studies of Type-A behaviour and hostility may be related to the coping subtypes of the subject sample. Further attempts to cross-validate this classification scheme and to examine its health-related correlates are needed.


Psychiatric morbidity in bus crews following violent assault: a follow-up study. In a prospective study 22 bus crews who were victims of physical assault were assessed using standardized psychiatric instruments, followed up for 18 months and compared to a non-assaulted control group drawn from the same bus garage. At initial assessment the assaulted group, compared to the controls showed a significant increase in psychiatric impairment and distress (as measured by the GHQ-30 and IES respectively), with 23% of assault victims developing post-traumatic stress disorder as defined by DSM-III-R. At follow-up, while high levels of both psychiatric impairment and distress persisted there was evidence that they may be separate phenomena.


From the jumping Frenchmen of Maine to post-traumatic stress disorder: the startle response in neuropsychiatry. The startle response is a universal and phylogenetically ancient reflex. Pathological exaggerations and modifications of startle underlie the symptomatology of a surprisingly diverse range of neuropsychiatric disorders, a fact that seems to have gone largely unappreciated. We review the available literature on the physiology of the normal human startle response and examine the neuropsychiatric conditions characterized by pathological startle. Startle epilepsy and primary hyperekplexia are considered as neurological disorders involving abnormal startle. Patients with hyperstartle and exotic culture-bound syndromes characterized by excessive startle are considered by the authors to represent extreme variants of the normal startle response. Post-traumatic stress disorder, drug and alcohol withdrawal states and schizophrenia all have abnormal startle as a clinical feature secondary to increased arousal and presumed disturbance of central neurotransmitter systems. The neurophysiological mechanisms by which abnormalities of the startle response may occur are discussed and a system of classification of neuropsychiatric hyperstartles is suggested.


A longitudinal study of general practitioner consultations for psychiatric disorders in adolescence. Patterns of psychiatric diagnoses given during adolescence to a group of individuals continuously registered with a single general practitioner in South London over 20 years were analysed first during 'early adolescence' and secondly during 'early adulthood'. Psychiatric diagnoses were found to be relatively common. Of the young adolescents who received a psychiatric diagnosis (almost one in ten of the group), 38% received a psychiatric diagnosis as young adults compared with only 16% of the remainder. Comorbidity was found to be very common--over 50% of young adults with a diagnosis of depression also had a diagnosis of anxiety and phobic neuroses. Young people with problems of a psychological nature therefore deserve more attention, particularly from the primary care team.


Labelling and illness in primary care: comparing factors influencing general practitioners' and psychiatrists' decisions regarding patient referral to mental illness services. GPs and psychiatrists from South Wales were asked to make decisions based on the information included in each of 16 vignettes describing depressed and anxious subjects. This information contained randomly assigned sex, psychiatric label, good and bad psychosocial context and age as well as eight different severity ratings of depression and anxiety symptoms. Our results showed that both GPs and psychiatrists were influenced in their decision making by the severity of the illness, but that GPs alone were also strongly influenced by the presence of male sex and by the presence of a psychiatric label. Good or bad psychosocial context had no influence on the GPs' referral decision, and previous experience in psychiatry or other vocational training had no detectable effect, but this may be because of the sample size.


QALYs in mental health: a case study.

QALYs in mental health: a case study. The applicability of the Charing Cross health indicator (CH-X) to the field of mental health was investigated in a community setting using descriptive statistics and principal components analysis. The CH-X is based on assessments of (i) distress and (ii) disability. Our results suggest that with respect to quality of life in mental health settings measurements of distress may be of greater importance than disability. In addition, the CH-X may be insensitive to variations in the severity of mental disorder and may primarily reflect physical disability as opposed to social disability. QALYs methodology may require the adoption of a multidimensional measure of health in order to fulfil its proposed role in comparing medical and mental health programmes.


The general population prevalence of non-organic psychiatric disorders in subjects aged 85 years and over. The prevalence of psychiatric disorders was investigated in all inhabitants over 85 years of age (N = 1259), residing in Leiden, The Netherlands. The study design consisted of two phases. In the first phase the Mini-Mental State Examination (MMSE) and the 12-item version of the General Health Questionnaire (GHQ-12) were used to screen for potential cases; in the second phase all potential cases and a sample of the non-cases were interviewed with the Geriatric Mental State Schedule (GMS). DSM-III diagnoses were made based on the GMS and on information obtained from caregivers. There was a high prevalence of organic disorders of 31% (95% CI: 27-35%). The estimated overall prevalence rate for functional disorders was 8% (95%) CI: 4-12%). This is an underestimate because organic and functional disorders are mutually exclusive in DSM-III. The prevalence rate estimated for the population at risk for functional disorders (i.e. the total population minus the organic cases) was 12% (95% CI: 6-18%). This is very similar to prevalence rates for functional disorders found in population based surveys in younger age groups. Therefore, in contrast with the dementias, there appears to be no increase with age for the functional disorders.


Social class and minor psychiatric disorder in British Civil Servants: a validated screening survey using the General Health Questionnaire. Major psychiatric disorder is more common in people of lower rather than higher socioeconomic status. This is less clear for the commoner, so-called minor psychiatric disorders, but these are more affected by tendency to report symptoms. To examine this the distribution of minor psychiatric disorder by employment grade measured by the 30-item General Health Questionnaire is reported from the first cross-sectional phase of the Whitehall II Study of 10,314 London-based civil servants, men and women between 35 and 55 years. Validation of the GHQ in a random subsample stratified by grade and sex (N = 201) suggested that people in lower employment grades tend to under-report minor psychiatric disorder on the GHQ relative to those in higher employment grades. The prevalence of minor psychiatric disorder corrected by the coefficients from the validity study was greater in the lower employment grades than the higher employment grades particularly for men. This was echoed in grade differences in well-being measured by the Affect Balance Scale, and in symptoms and recurrent health problems. Overall, for women there were few clear-cut differences in minor psychiatric disorder by employment grade. The lack of social class gradient in women suggests that further exploration should examine women's role at work and their personal lives for the aetiology of minor psychiatric disorder.


Mental health effects of job loss in women. This paper reviews literature on the mental health effects of involuntary job loss among women. In addition, a prospective study of the effects of job loss on psychological distress in a cohort of blue-collar women is described. A total of 141 women, of whom 73 were laid off during the 12-month study period, were examined. The occurrence and duration of lay-off was significantly associated with increased depressive symptoms, but not anxiety-related symptoms, even after effects of pre-lay-off psychological symptoms, social supports and occupational stress were considered. There was no evidence that these effects of lay-off were moderated by other characteristics measured prior to lay-off. Among women who were laid off, those who reported poor levels of support from their husband or partner in the immediate aftermath of lay-off and those experiencing more financial difficulties during the lay-off had higher depression levels at follow-up. The nature of the lay-off as a chronic psychosocial stressor is discussed.


'Mentally disordered persons found in public places'. Diagnostic and social aspects of police referrals (Section 136). A survey over 2 years of all Police Referrals (Section 136 of the Mental Health Act 1983) in an inner-city health district identified 163 cases, with a core group of repeat referrals. Previous psychiatric admissions, a diagnosis of schizophrenia, social deprivation, and a bias towards young men of Afro-Caribbean ethnicity were key features. The difficulty of obtaining clear data and uncertainties within the law rebound unfairly on patients, police and psychiatrists. Section 136, while not inappropriate diagnostically, can be seen as highlighting unmet social and medical needs in the context of community care. The requirement for coordinated resources, including acute in-patient services sufficient for deprived populations and legal provision for treatment beyond a hospital's boundaries, seems paramount.


The use of the Ways of Coping (Revised) questionnaire with parents of children with Down's syndrome. The principal aim of this study was to assess the validity and usefulness of the Ways of Coping (Revised) questionnaire (Folkman & Lazarus, 1985) with a British sample of parents of children with Down's syndrome. Factor analysis yielded five subscales which were compared with those reported elsewhere. Other properties of the instrument were investigated. It was concluded that the instrument was potentially valuable to those investigating coping in families with special problems.


Cotard delusion after brain injury.

Cotard delusion after brain injury. A right-handed young man with contusions affecting temporo-parietal areas of the right cerebral hemisphere and some bilateral frontal lobe damage became convinced that he was dead (the Cotard delusion), and experienced difficulties in recognizing familiar faces, buildings and places, as well as feelings of derealization. Neuropsychological investigation while these symptoms were resolving revealed impairment on face processing tests. We suggest that these impairments contributed to his Cotard delusion by heightening feelings of unreality, and that the underlying pathophysiology and neuropsychology of the Cotard delusion may be related to other problems involving delusional misidentification.


Family dysfunction as a risk factor in the development of antisocial behavior. Many studies have indicated a positive correlation between family dysfunction and subsequent cognitive and behavioral problems in offspring. The purpose of this study was to compare the family histories of 118 inmates with those of 45 college students and to document differential patterns. The possible social implications of the data are discussed as well as directions for further research.


Need for achievement and performance on measures of behavioral fluency. This investigation was designed to assess the relationship between a validated personality characteristic, need for achievement (nAch), and performance on measures of behavioral fluency. To infer this relationship, 50 neurologically intact college undergraduates were administered a questionnaire assessing nAch and a battery of tests including a short form of the WAIS and measures of behavioral fluency (i.e., verbal fluency). Statistical analysis indicated that subjects high on nAch obtained higher scores than subjects low on nAch on the measures of figural fluency and the WAIS Verbal Scale. No significant difference on verbal fluency was seen between the two groups. Secondly, the group high on nAch also had a higher mean Verbal IQ but not a higher mean Performance IQ as measured by a short form of the WAIS than did subjects scoring low on nAch.


WAIS-R scatter with psychiatric inpatients: I Intrasubtest scatter. Intrasubtest scatter values for eight WAIS-R subtests were estimated for a sample of 150 psychiatric inpatients and compared with those reported for a comparable portion of the WAIS-R standardization group by Kaplan, Fein, Morris, and Delis in 1991, using the normal deviate (z) test. The standardization group's intrasubtest scatter was significantly greater than those reported for the psychiatric inpatients on all subtests except Arithmetic and Information. These results suggested that, contrary to expectation, limited intrasubtest scatter may characterize WAIS-R protocols of psychiatric inpatients, while the presence of scatter may characterize normal WAIS-R performance.


Validity of the Threat Index.

Validity of the Threat Index. The validity of the Threat Index was examined in a study of 42 students and 15 HIV+ clients. When completing the Threat Index, subjects rate the self and death on 30 bipolar adjectives. A count is made of the number of times the same adjective poles are used to describe the self and death. Uses of the same poles are called matches, while uses of different poles are called splits. The Threat Index is based on the assumption that splits indicate threat. Analysis showed that neither splits nor matches were usually threatening and that neither was necessary or sufficient for the experience of threat. These results did not support the validity of the Threat Index.


Moral development and behavior.

Moral development and behavior. The study of moral development as well as the relation of moral development and behavior has been of great interest to many over the past half a century. While some studies have shown no association between one's moral development and behavior, some evidence indicates level of moral reasoning influences behavior. Over 16 selected studies postconventional principles of justice are likely to be more prosocial and law-abiding than those appropriate at the lower stages of moral development.


Scores on the State-Trait Anxiety Inventory for children in a longitudinal study of pubertal Spanish youth. Changes in scores on the State-Trait Anxiety Inventory for Children for a sample of 534 pubertal adolescents were longitudinally studied over a period of 4 years. Biological development and other variables were investigated. For the 310 boys, A-trait scores decreased significantly with age. The 224 girls showed significantly higher scores than boys in all years of the study. No significant relationship was found between anxiety and pubertal maturity. The year-to-year persistence in symptomatology of anxiety ranged between 55.6% and 66.1% for girls and between 48.5% and 53.1% for boys. Girls showed bi- and tri-annual persistence between 31% and 50%, and boys between 13% and 27%. Neuroticism scores formed the best predictor of A-trait scores. Symptomatology of anxiety is not transient during early adolescence, so personality may provide a risk indicator in the development of anxiety.


Jewish inmates: an atypical prison group. 12 Jewish inmates scored significantly higher than 1497 non-Jewish inmates on a measure of intelligence, the Raven's Standard Progressive Matrices. Interview findings indicated that the present Jewish inmates were never very involved in the practice of Judaisn and were not strongly integrated into their local Jewish communities.


Inferred and expressed self-image of pupils rated by teachers as high and low in anxiety: a comparison of self-other ratings. The association was examined between 98 third-grade pupils' expressed self-image scores and inferred self-image ratings from teachers. Significant self-other agreements were found with sexes combined. With sexes separated, significant self-other agreements were found for the 52 girls, but not for the 46 boys.


Longitudinal examination of teachers' burnout in a school district. Teachers in a rural school district were administered the Maslach Burnout Inventory three times over a five-year period. Teachers scoring high on emotional exhaustion and low on personal accomplishment were classified as "experiencing burnout." Across the three waves, the proportion of teachers meeting these criteria for burnout were 7%, 11%, and 11%, respectively. By grade, burnout was noted among 3%, 8%, and 9%, respectively, over time for senior high-school teachers; 7%, 7%, and 11% for junior high-school teachers; and 9%, 17%, and 12% for elementary school teachers. Interventions must consider grade-taught and are probably most cost-effective for elementary school. It is important to establish norms across time and across school settings to determine high-risk groups deserving interventions.


Stability of parental nurturance as a salient predictor of self-esteem. The relationship of parental nurturance to self-esteem for seven distinct adolescent and early-adulthood age groups (N = 784) was investigated. Analysis showed that even though mothers' and fathers' nurturance together were more strongly related to self-esteem during the junior high school years (R2 values greater than 50% were obtained in each of the junior high samples) than during the high school and college years (R2 values less than 40% were obtained in each of these samples), parental nurturance still remained a robust predictor of self-esteem during these latter years. These results were discussed within the context of (a) the stability at different ages of the bases upon which one's judgments of self-esteem are made, and (b) parental nurturance as a stabilizing influence during the transitional years of adolescence and early adulthood.


Evaluation of an intervention designed to improve patients' hospital experience. The influence of a videotape, shown in a hospital admitting room, on patients' state anxiety and concerns about hospitalization was assessed in a preliminary study. For both state anxiety and specific concerns regarding hospitalization the pretest scores on each variable accounted for the preponderance of the variance in the posttest scores. In both instances, the intervention and the interaction of the intervention with the pretest scores accounted for less than 1% of variance in the outcome. While finding small effects to be significant for such a small sample (N = 93) is unlikely, the sample size was adequate to detect medium to large effects. More important was the fact that 73.33% of the videotape intervention group indicated that they did not watch the video, which leads us to the conclusion that this intervention as tested is not worthwhile.


Mental health locus of control in first-degree relatives of agoraphobic and depressed inpatients. Mental health locus of control in 77 first-degree relatives of agoraphobic, agoraphobic and major depressed (comorbid), and depressed inpatients were studied. Relatives of comorbid patients externalized locus of control more to chance than did relatives of agoraphobic and of depressed patients. These results suggest that a tendency to externalize to chance is familially transmitted and may be a vulnerability factor for the development of the comorbid condition of agoraphobia and major depression.


Summer and school-term youth employment: ecological and longitudinal analyses. The effects of summer versus school-year employment on self-esteem, peer relationships, and family social climate were investigated in a sample of 135 adolescents. Students were assessed the summer before entrance into high school and during the second semester of high school, using a longitudinal design. Cross-sectional findings indicated that, during the summer, 52 workers possessed higher self-esteem than 79 nonworkers. Longitudinal analysis indicated that 10 girls who worked only during the school term reported increases in both stress and activity with peers. At our final assessment, the families of 49 students who did not work at either time had become more conflicted and less cohesive than families of all other students. The developmental implications of these results are discussed.


Perception of political candidates based on their stand on abortion and taxes. This study investigated whether young voters would vote for and volunteer to work for the election campaign of a presidential candidate, given the candidate's background and positions on two major campaign issues. Findings indicate that, although voter-candidate agreement on a single issue may be enough for a voter to vote for a candidate, agreement on both issues may be necessary before a voter agrees to volunteer to work for the candidate's election campaign.


Relationships among critical thinking skills, academic achievement, and misconceptions about psychology. Two groups of 60 students each were selected from introductory college psychology classes. One consisted of high academic achievers, the other of average achievers. They were given the McCutcheon Test of Misconceptions, a 65-item, multiple-choice test designed to measure common misconceptions about psychology. Subsequently, they were also given the Watson-Glaser Critical Thinking Appraisal. Both groups made many errors on the McCutcheon test, but high academic achievers made significantly fewer errors on both the McCutcheon test and the Watson-Glaser than average achievers. A stepwise multiple regression consisting of Watson-Glaser subscales 1 (the ability to draw valid inferences) and 4 (ability to weigh and interpret evidence) and GPA successfully predicted McCutcheon test scores (R = .43). This suggests that even beginning students with high grades and good critical thinking skills are likely to harbor many misconceptions about psychology.


Students' knowledge of AIDS and sexual risk behavior. College students appear to be knowledgeable of the methods of transmission and risks of the AIDS virus. However, the reality of susceptibility to infection does not seem to have altered their conduct. In a study of 19 heterosexual college students, knowledge and intention do not appear to be good predictors of sexual behavior. Young people appear to continue high-risk sexual behavior even while knowledgeable of the risks of AIDS.


Alcohol and creative writing.

Alcohol and creative writing. A repeated-measures design was used to test for the effects of alcohol on creative writing as measured by use of novel figurative language. 11 male social drinkers participated in a creative writing task under two conditions, alcohol (high dose: 1.1 ml. ethanol/kilogram body weight) and placebo. In the alcohol condition, within-subject comparisons indicated significantly greater quantity of creative writing while intoxicated. These results were interpreted as supporting the belief that alcohol can reduce "writer's block," at least amongst nonalcoholic subjects.


Assessment of preschoolers at-risk with the WPPSI--R and the Stanford-Binet L-M. The purpose of this study was to provide data on the validity of using the WPPSI--R with 16 preschoolers who had been referred for psychological assessment. A comparison of the preschoolers' performance on the WPPSI--R and the Stanford-Binet L-M was made. Children ranged in age from 3-0 to 6-0 years, with a mean age of 4-5 yr. The correlations between WPPSI--R and Stanford-Binet L-M scores were strong; WPPSI--R Verbal IQ and Stanford-Binet L-M IQ, r = .85; WPPSI--R Performance IQ and Stanford-Binet L-M IQ, r = .75, and WPPSI--R Full Scale IQ and Stanford-Binet L-M IQ, r = .82. For this very small sample of children whose mean IQ was significantly below average, the WPPSI--R appeared to assess validly their current intellectual functioning. Attention should be given concurrent and predictive validity as well as the efficiency of using the WPPSI--R with other and larger samples of referred children.


Reliability data for a Greek translation of the Revised UCLA Loneliness Scale: comparisons with data from the USA. A Greek translation of the Revised UCLA Loneliness Scale was internally reliable (alpha = .89), after eliminating Item 4, and significantly correlated with the English version (r = .94) for a sample of bilingual students. Weiss's distinction between social loneliness and emotional loneliness was also reliably identified in the Greek translation. Loneliness scores in Greece were significantly higher than in the USA. The translation seems to be sufficiently reliable to warrant further use with Greek individuals.


Behavioral economics of drug self-administration. III. A reanalysis of the nicotine regulation hypothesis. The maintenance of a characteristic level of nicotine in a smoker's body is referred to as nicotine regulation. Considerable research has examined this question of whether smokers regulate nicotine intake. This is because nicotine regulation raises the question of whether smokers who, to decrease their intake of tar, switch to low tar/low nicotine cigarettes will increase the number and/or intensity of cigarettes smoked. Although the results of studies examining nicotine regulation are reported as generally consistent, considerable variability exists across these analyses such that the health hazards of smoking low tar/nicotine cigarettes remains uncertain. In the present analysis, these studies were analyzed to ascertain whether a behavioral-economic interpretation could better quantify the effects of changing nicotine yield on individuals' nicotine and smoke consumption. Specifically, 17 nicotine-regulation studies were reanalyzed using a unit-price analysis (i.e., cost-benefit analysis). The reanalysis showed less variability across regulation studies than previously reported; a positively-decelerating demand curve was found across most studies, consistent with previous unit-price analyses of food- and drug-maintained behavior. The benefits of this reanalysis versus the traditional regulation interpretation are that the behavioral economics approach: 1) brings unity to a variable set of data, 2) shows a nonlinear relationship, previously considered to be linear, between nicotine consumption and nicotine yield, 3) shows that nicotine yields higher, and not lower, than the smoker's usual brand decrease smoke consumption and thus decreases consumption of the harmful agents in tobacco, 4) better quantifies the data and provides a more parsimonious interpretation that generalizes to other drugs and food-maintained behavior in humans and nonhumans and, 5) integrates behavioral and pharmacological factors that control the consumption of reinforcers. These results suggest the value of behavioral economics in the study of consumptive behaviors and clinically suggest, in agreement with the studies contained herein, that decreasing the smoker's usual nicotine yield can have potential health risks for smokers who are unable to stop smoking.


Effects of a single dose of the acetylcholinesterase inhibitor velnacrine on recognition memory and regional cerebral blood flow in Alzheimer's disease. The effects of a single oral dose of the acetylcholinesterase inhibitor velnacrine maleate on word and object recognition memory and regional uptake of 99mTc-exametazime were examined in patients with Alzheimer's disease. Word recognition memory was marginally improved 2 h after 75 mg velnacrine. With the same dose of velnacrine a relative increase in superior frontal uptake of 99mTc-exametazime was shown with single photon emission computed tomography (SPECT). This suggests increased regional perfusion and metabolism as a consequence of cholinergic stimulation. The effect did not co-vary with the degree of memory improvement, but, instead, more cognitively impaired patients showed a greater increase in tracer uptake after velnacrine, suggesting cholinergic hypersensitivity in the brains of Alzheimer patients.


Elevated corticosteroid levels block the memory-improving effects of nootropics and cholinomimetics. Oral pretreatment of mice with aldosterone or corticosterone blocked the memory-enhancing effects of piracetam, pramiracetam, aniracetam and oxiracetam in a dose-related manner, without, however, impairing the animals' learning performance. The improvement of memory induced by physostigmine, arecoline, and tacrine (THA) was similarly inhibited. The fact that elevated steroid levels suppress the memory-enhancing effects of entirely different substances could indicate that these substances have a common site of action. In the light of new observations showing increased cortisol concentrations in Alzheimer patients, this steroid dependency of the effects of memory enhancers might explain why only a limited number of these patients respond to therapy with nootropics or cholinomimetics.


Attenuation of chemically induced defence response by 5-HT1 receptor agonists administered into the periaqueductal gray. The ability of 5-HT1 receptor agonists to modulate a chemically induced defence response has been studied in Lister hooded rats. Microinjections of the excitatory amino acid D,L-homocysteic acid (DLH) in both rostral and caudal dorsal periaqueductal gray matter (PAG) caused explosive motor behaviour characteristic of defence. This behaviour was quantified in terms of response duration, arena revolutions and number of defensive jumps. Direct administration into the PAG of either 5-carboxamidotryptamine (5-CT) or 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT) produced behaviours (decreased exploratory rearing, dose related onset of flat body posture) indicative of 5-HT1A receptor activation. Pretreatment with either 5-CT or 8-OHDPAT directly in the PAG caused a significant attenuation, and in some cases a complete abolition, of the DLH evoked response. These agonists share high affinity in vitro for the 5-HT1A receptor. Thus the results suggest that in vivo activation of 5-HT1A receptors mediates an antiaversive response with respect to defensive behaviour elicited by specific chemical stimulation of the dorsal PAG.


Interaction of sigma and PCP-like drugs on operant behaviors in the rat. Many PCP-like drugs interact with at least two types of binding sites in the CNS, one of which is linked to excitatory amino acid transmission and the other with an unknown function. The present experiments were designed to further clarify the mechanism of action of drugs in this class. Assessment was made of the effects of PCP, MK-801, (+)-pentazocine, (+)- and (-)-N-allyl-normetazocine (NANM), (+)-amphetamine and BMY-14802 in rats responding under a multiple timeout 600 s (TO), differential reinforcement of low rates 10 s (DRL), fixed ratio (FR) 10 schedule of reinforcement. The effects of the PCP-receptor selective drug MK-801 were compared to those of the mixed sigma/PCP drug (+)-NANM after each were combined with doses of (+)-pentazocine, PCP, BMY-14802, and (+)-amphetamine. MK-801 was also tested in combination with (+)-NANM, as was PCP with BMY-14802. When administered alone, MK-801, PCP, (+)-NANM, (+)-pentazocine, and (+)-amphetamine increased rates of responding under the DRL component of the multiple schedule. The drugs tested generally produced decreases in rates of responding under the FR component. (+)-Pentazocine and BMY-14802 did not modify the effects of (+)-NANM or of MK-801. PCP enhanced the effects of MK-801 and (+)-NANM, and (+)-amphetamine enhanced the effects of MK-801 but not of (+)-NANM. BMY-14802 attenuated the effects of PCP. Taken together, these data suggest similarities as well as some differences in the pharmacologic activities of MK-801 and (+)-NANM and PCP.


Role of spinal serotonin1 receptor subtypes in thermally and mechanically elicited nociceptive reflexes. The ability of 5-HT1A and 5-HT1B agonists to alter a spinal animal's nociceptive threshold was examined using two analgesiometric tests. In the spinal withdrawal reflex test, administration of the selective 5-HT1A agonists ipsapirone, gepirone and PAPP resulted in significant dose-dependent increases in receptive field (RF) area for withdrawal reflexes when compared to predrug baseline values, indicating an increase in nociceptive sensitivity. The average overall percent maximal increase in RF area following administration of 5-HT1A selective compounds was: 80 +/- 16% for the ventroflexion reflex, 90 +/- 6% for the dorsiflexion reflex and 87 +/- 8% for the lateral flexion reflex. Similar to the effects noted with 5-HT1A agonists, administration of 5-HT1B agonists RU24969, mCPP and TFMPP resulted in a hyperalgesic response with an overall percent maximal increase of 43 +/- 6% for the ventroflexion reflex, 51 +/- 6% for the dorsiflexion reflex and 38 +/- 9% for the lateral flexion reflex. In the tail-flick analgesiometric test, administration of the 5-HT1A agonists 8-OH-DPAT and ipsapirone and the 5-HT1B agonists RU24969 and mCPP resulted in a significant dose-dependent increase in tail-flick latencies when compared to predrug baseline values, indicating a decrease in nociceptive sensitivity to noxious thermal stimuli. No differences in magnitude of the effect of the two receptor subtypes were found, indicating that stimulation of either 5-HT1A or 5-HT1B receptors was equipotent in producing the antinociceptive tail-flick response.(ABSTRACT TRUNCATED AT 250 WORDS)