spe-29 encodes a small predicted membrane protein required for the initiation of sperm activation in Caenorhabditis elegans.

Caenorhabditis elegans spermatids complete a dramatic morphogenesis to crawling spermatozoa in the absence of an actin- or tubulin-based cytoskeleton and without synthesizing new gene products. Mutations in three genes (spe-8, spe-12, and spe-27) prevent the initiation of this morphogenesis, termed activation. Males with mutations in any of these genes are fertile. By contrast, mutant hermaphrodites are self-sterile when unmated due to a failure in spermatid activation. Intriguingly, mutant hermaphrodites form functional spermatozoa and become self-fertile upon mating, suggesting that spermatids can be activated by male seminal fluid. Here we describe a mutation in a fourth gene, spe-29, which mimics the phenotype of spe-8, spe-12, and spe-27 mutants. spe-29 sperm are defective in the initiation of hermaphrodite sperm activation, yet they maintain the ability to complete the morphogenetic rearrangements that follow. Mutant alleles of spe-12, spe-27, and spe-29 exhibit genetic interactions that suggest that the wild-type products of these genes function in a common signaling pathway to initiate sperm activation. We have identified the spe-29 gene, which is expressed specifically in the sperm-producing germ line and is predicted to encode a small, novel transmembrane protein.

Physicians' attitudes about involvement in lethal injection for capital punishment.

BACKGROUND: Physicians could play various roles in carrying out capital punishment via lethal injection. Medical societies like the American Medical Association (AMA) and American College of Physicians have established which roles are acceptable and which are disallowed. No one has explored physicians' attitudes toward their potential roles in this process. METHODS: We surveyed physicians about how acceptable it was for physicians to engage in 8 actions disallowed by the AMA and 4 allowed actions involving lethal injection. Questions assessing attitudes toward capital punishment and assisted suicide were included. The impact of attitudinal and demographic variables on the number of disallowed actions deemed acceptable was analyzed via analysis of variance and multiple logistic regression analysis. RESULTS: Four hundred eighty-two physicians (51%) returned questionnaires. Eighty percent indicated that at least 1 of the disallowed actions was acceptable, 53% indicated that 5 or more were acceptable, and 34% approved all 8 disallowed actions. The percentage of respondents approving of disallowed actions varied from 43% for injecting lethal drugs to 74% for determining when death occurred. All 4 allowed actions were deemed acceptable by the majority of respondents. Favoring the death penalty (P<.001) and the acceptance of assisted suicide (P<.001) were associated with an increased number of disallowed actions that were deemed acceptable. CONCLUSIONS: Despite medical society policies, the majority of physicians surveyed approved of most disallowed actions involving capital punishment, indicating that they believed it is acceptable in some circumstances for physicians to kill individuals against their wishes. It is possible that the lack of stigmatization by colleagues allows physicians to engage in such practices. Arch Intern Med. 2000;160:2912-2916

Confidentiality and health insurance fraud.

BACKGROUND: Health insurance fraud committed by patients may be an increasing problem given the number of underinsured and uninsured people in the United States. Physicians recognizing acts of health insurance fraud perpetrated by patients face an ethical dilemma: should they disclose the incident to the insurance company, or protect patient confidentiality? OBJECTIVE: To explore physicians' attitudes toward the reporting of patient-initiated health insurance fraud. METHODS: Three hundred seven physician members of the American College of Physicians returned a mailed questionnaire that presented 6 case vignettes (3 variables) of patients who used a relative's insurance to obtain health care in the past. For each vignette, respondents were asked whether the treating physician should report insurance fraud to the health insurance carrier. RESULTS: Sixty-three respondents (20.7%) indicated that physicians should report all the patients presented in the vignettes, while 45 (14.8%) indicated none should be reported; the rest indicated that the decisions to-report should be based on the characteristics presented, with acute vs terminal illness (P < .001), history of fraud (P < .001), and wealth of the patient (P < .001) all causing physicians to be more likely to report the patient to the health insurance carrier. Multivariate analysis demonstrated that type of practice (P = .04) and respondents' experiences with insurance fraud (P = .03) had significant effects on the willingness to report patients. CONCLUSIONS: Physicians are divided about whether to report patients who have committed insurance fraud. Their decisions to report insurance fraud are influenced by their attitudes and demographic features, as well as by patient factors.

The decision to hospitalize.

The authors explored determinants of psychiatric hospitalization in four Manhattan general hospital emergency rooms and found that although the nature and severity of a patient's problem played the most important role in the decision to hospitalize, the facility involved was also a determining factor. The findings are discussed in relation to policy concerning staffing and organization of emergency room services and future studies of service delivery in this area.

Biochemical evidence for cholinergic activity in retinal blood vessels.

Blood vessels from human, cat, pig and bovine retinas were analyzed for their contents of choline acetyltransferase (ChAT) and muscarinic binding sites. ChAT was measured by the synthesis of 3H-acetylcholine in the presence of 3H-acetyl CoA and choline. Muscarinic binding sites were determined by the specific binding of 3H-quinuclidinyl benzylate (3H-QNB). Tissue levels of ChAT varied from 39-850 nmol/g/hr, the lowest values being in human tissues. Muscarinic binding sites were less different (0.5 to 1.8 fmol/mg net weight) among the species studied, being the highest values in human retinal vessels. It appears that retinal blood vessels not only have sites to bind acetylcholine, perhaps to mediate physiologic responses, but might be capable of supplying acetylcholine for local vascular tone control.

Descending optic nerve degeneration in primates.

We cut the optic nerve at the orbital apex in squirrel monkeys to study the descending degeneration of optic nerve axons and their ganglion cell bodies. We could not detect progressive disintegration of the axon from the site of injury back to the cell body. Instead, the entire length of individual axons seemed to degenerate simultaneously as early as 3 weeks and as late as 6 weeks after injury, as judged both by ultrastructural integrity and by continued slow axonal transport, a reflection of local physiologic function. We could not relate the time of degeneration to the distance of the injury from the cell body. Evidently there is a signal of injury to the cell body after axotomy, though the nature of the signal and the mechanism by which it leads to cell death are unknown.

Angiotensin II binding receptors in retinal and optic nerve head blood vessels. An autoradiographic approach.

Angiotensin II (AII) binding sites were identified in cross-sections of the cat retinal and optic nerve vasculatures. The authors used 3H-AII and 125I-saralasin, an agonist and a high-affinity antagonist of AII receptors, respectively, to generate light microscopy autoradiograms in resin-embedded tissues. With both radioligands the presence of AII binding sites was confirmed in retinal arterioles but not in the veins or capillaries of the retina. Additionally the presence of such binding sites in the capillaries of the optic nerve head was shown. These results support the hypothesis that microvascular tone and perhaps autoregulatory responses of optic nerve capillaries might be influenced by vasoactive substances, such as AII, either leaking from the choroid or locally synthetized.

Response of retinal vasculature to phenylephrine.

In a freshly enucleated bovine eye, the retinal arteries and veins constrict when phenylephrine is applied directly on the surface of the vessel walls. This "in situ" preparation allowed us to observe the reaction of retinal vessels without any surgical procedure that might alter the vascular response to agonists. These results indicate that alpha1-adrenergic receptors are present in the retinal vessels, which might therefore respond to vasoactive hormones. If, when, and how these reactions occur is still to be studied.

The response of retinal vasculature to angiotensin.

A retinal arterial constriction was produced in anesthetized cats with a continuous transvitreal infusion of angiotensin I or angiotensin II (Ile-5). Constriction of vessels near the infusion cannula tip occurred over a range of angiotensin II concentrations from 10(-9) to 10(-4) molar, and was reversibly blocked by a ten-fold excess of the competitive antagonist saralasin. Constriction did not occur in response to angiotensin I if angiotensin-converting enzyme was blocked with Captopril. Control infusions of saline did not elicit a contraction of the retinal arteries. Severe axonal and inner retinal damage and necrosis occurred when angiotensin II produced a prolonged vasospasm, but not after infusion with control solutions, or when-constriction caused by angiotensin was brief.

Effects of cholinergic and adrenergic agonists on adenylate cyclase activity of retinal microvascular pericytes in culture.

Pericytes are contractile cells that might help regulate microvascular blood flow. To understand their potential role in the regulatory responses of the retina and optic nerve head vessels, the response of pericytes isolated from bovine retinal microvessels was determined to oxotremorine, isoproterenol, phenylephrine, and clonidine. Isoproterenol doubled the basal levels of cyclic adenosine monophosphate (cAMP) specifically through beta-adrenergic receptors, because the effect was blocked by dl-propranolol. The alpha 1 agonist phenylephrine did not induce any major change in adenylate cyclase activity. The alpha 2 agonist clonidine decreased basal cAMP synthesis and reduced the effect of isoproterenol. The cholinergic agonist oxotremorine did not modify the basal activity of adenylate cyclase but was able to decrease by almost 50% the forskolin-induced increase of cAMP. These results suggest that pericytes have functional adrenergic and cholinergic receptors, and they might respond to autonomic vasoactive substances present in vivo.

Angiotensin binding sites in bovine and human retinal blood vessels.

Blood vessels isolated from bovine and human retinas have sites that specifically bind 3H-angiotensin II (3H-Ag II) with an apparent dissociation constant (Kd) of 14 nM and a capacity of binding (Bmax) of 0.82 pmol/g. The binding sites for 3H-Ag II appear to be influenced by guanine nucleotides (GTP) and cations (Mg2+ and Na+) in a way that resembles angiotensin II receptors in other tissues. The physiologic effect of blood-borne or locally-formed angiotensin II on retinal blood flow remains to be defined.

Angiotensin-converting enzyme in bovine, feline, and human ocular tissues.

Angiotensin-converting enzyme was shown to be present in retinal vessels and neural retina of feline, bovine, and human eyes. It was also demonstrated in the other ocular tissues of feline eyes, in especially high concentration in the highly vascular uveal layer. Its role in the physiology of ocular blood flow and neurophysiology is uncertain, especially in the retina where circulating angiotensin and bradykinin are confined to the intravascular space by the blood-retina barrier, and sufficient data are not available to describe these peptides as transmitters or modulator molecules in the retina.

Sensitivities of ocular tissues to acute pressure-induced ischemia.

Intraocular pressure was artificially elevated for eight hours in eight owl monkeys. The first permanent effect (produced at a perfusion pressure of plus 15 mm Hg) was partial necrosis of iris stroma and ciliary processes, associated with microscopic lesions in the photoreceptors and retina pigment epithelium around the disc and in the retinal periphery. At a slightly higher pressure, visual nerve fibers in the retina and optic nerve and their ganglion cells were affected. Simultaneously, the outer retinal layers showed damage to the pigment epithelium, photoreceptors, and other nuclear layers. At even higher pressures, nearly all the other intraocular tissues were affected except for Müller cells, astroglia in the optic nerve head, epithelium of the pars plana, and the pigment cells of the choroid. The possibility is raised of a nonischemic pressure-induced mechanism for destruction of disc astrocytes in human chronic glaucoma.

Modified goniotomy for inflammatory glaucoma. Histologic evidence for the mechanism of pressure reduction.

A modified goniotomy (trabeculodialysis) was performed on both eyes of a 33-year-old woman who had glaucoma secondary to sarcoid uveitis. One month after trabeculodialysis, a cataract extraction was performed on one eye and a histologic specimen was obtained from the area of the filtration angle that was previously incised. Successful control of intraocular pressure has been maintained in both eyes for 18 months following trabeculodialysis. By light and electron microscopic examination, there was a nonhealed incision between the anterior chamber and Schlemm's canal. Trabeculodialysis, it is concluded, works by providing direct communication between the anterior chamber and Schlemm's canal, and might be effective in all trabecular obstructive glaucoma of short duration before secondary changes occur in the outer drainage channels.

Herpes simplex retinitis.

Fatal encephalitis with accompanying retinitis developed in a previously healthy 18-month-old infant. Clinically the disease appeared as whitish-yellow punctate lesions, perivascular cuffing, and hemorrhage. The antibody titer to herpes simplex rose from 1:8 on the day of admission to 1:256 on the day of death. Postmortem, intranuclear inclusion bodies that were typical of those found with herpesvirus were seen in the brain and retina. Viral particles consistent with those of herpesvirus were found by electron microscopy in the brain and in the inner-nuclear and ganglion-nerve fiber layers of the retina. This demonstrates the direct infectious nature of herpetic retinitis. Hematogenous spread of the virus to the retina is presumed.

A clinical, fluorescein angiographic, and electron microscopic correlation of cystoid macular edema.

Electron microscopic findings in an eye removed from a woman who had biomicroscopic and angiographic signs of cystoid macular edema occurring in association with a peripheral choroidal melanoma disclosed evidence that the anatomic basis for the biomicroscopic and angiographic changes was the polycystic expansion of the extravascular compartment of the retina by serous exudate and not, as previously reported, edema of the Mueller's cells.

Creating smaller eyedrops by reducing eyedropper tip dimensions.

The risk of toxicity and adverse systemic effects from eyedrops is increased because of the large size of conventional eyedrops. Although the tear film normally contains only 7 to 10 microliters, commercial eyedrops are 50 to 70 microliters. Much of the excess is pumped into the nasolacrimal system where it is systemically absorbed and capable of causing toxicity. A smaller eyedrop can achieve a maximal tear film concentration with far less systemic absorption. We found that changes in the outer and inner diameters of an eyedropper tip can alter eyedrop volume markedly. By selecting appropriate tip dimensions we produced eyedrops of less than 25 microliters; in some cases they were as small as 11 microliters.

Sequential chemotherapy and radiotherapy for squamous cell esophageal carcinoma.

A Phase II study of sequential chemotherapy with 5-fluorouracil and cisplatin followed by radiotherapy was initiated to see whether the use of two therapies sequentially could have an effect on response rate. Thirteen patients with advanced squamous cell carcinoma of the esophagus were treated with 1,000 mg/m2/day 5-fluorouracil days 1-5 continuously and 100 mg/m2 cisplatin on day 1. An average of four cycles (range, one to nine) were given every 28 days; 11 patients received more than three cycles. The radiation consisted of 60 Gy over 6-8 weeks. There was only one (8%) complete response (CR) and 11 (85%) partial responses (PRs). Restaging after radiation revealed no conversion of PR to CR. Median survival was 39 weeks (range, 6-208+). Chemotherapy alone or its use sequentially with radiotherapy is inadequate, and newer approaches are needed to to improve survival.

Mental illness in blacks: an overview, and treatment approaches.

Provisions for inner city mental health services must recognize the association between poverty, discrimination, and related social and physical conditions and disproportionately high rates of severe mental disorder-a transcultural phenomenon.Program emphasis should therefore be on the prevention, early recognition, prompt and effective treatment and rehabilitative care of psychosis. The total spectrum of psychiatric services is required for this, and thus an opportunity is afforded for necessary training and research.Poverty has negative impact on general health and cognitive development as well as on self-esteem, self-care, and the ability to utilize medical and health services. This contributes to a vicious, intergenerational poverty cycle.Primary prevention of mental illness, where possible, depends at present on socioeconomic change. Secondary prevention, ie, timely, appropriate treatment, is effective, but requires patient access to and acceptance of all indicated modalities of care.

Outcomes of care systems for chronic patients.

In a study of the postdischarge treatment of 119 comparable chronic schizophrenics hospitalized and treated after release in six community mental health care systems, it was found that lower rehospitalization rates and longer community survivorship correlated significantly with patients' compliance in early postdischarge treatment plans and the frequency of aftercare visits prescribed for them during the early postrelease period. Rehospitalization rates and community survivorship experience were substantially better for patients of two of the six systems, without disproportionate reduction of their clinical or social functioning in the community. Characteristics of the community care systems with better outcomes are described.